Pralsetinib

Identification

Summary

Pralsetinib is a RET receptor tyrosine kinase inhibitor for the treatment of metastatic RET-driven non-small cell lung cancer.

Brand Names

Gavreto

Generic Name

Pralsetinib

DrugBank Accession Number

DB15822

Background

Pralsetinib, similar to the previously approved selpercatinib, is a kinase inhibitor with enhanced specificity for RET tyrosine kinase receptors (RTKs) over other RTK classes.^3,5,9 Enhanced RET (Rearranged during transfection) oncogene expression is a hallmark of many cancers, including non-small cell lung cancer. Although multikinase inhibitors, including cabozantinib, ponatinib, sorafenib, sunitinib, and vandetanib, have shown efficacy in RET-driven cancers, their lack of specificity is generally associated with substantial toxicity.³ Pralsetinib (BLU-667) and selpercatinib (LOXO-292) represent the first generation of specific RET RTK inhibitors for the treatment of RET-driven cancers.^1,3,9

Although a phase 1/2 trial of pralsetinib termed ARROW (NCT03037385) is still ongoing, pralsetinib was granted accelerated FDA approval on September 4, 2020, for the treatment of metastatic RET-fusion positive non-small cell lung cancer. It is currently marketed under the brand name GAVRETO™ by Blueprint Medicines.⁹

Type

Small Molecule

Groups

Approved, Investigational

Structure

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MOLSDFPDBSMILESInChI

Similar Structures

Structure for Pralsetinib (DB15822)

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Weight

Average: 533.612
Monoisotopic: 533.266299469

Chemical Formula

C₂₇H₃₂FN₉O₂

Synonyms

• Pralsetinib

External IDs

• BLU 667
• BLU-123244
• BLU-667
• BLU123244
• WHO 11004
• X-581238
• X581238

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Pharmacology

Indication

Pralsetinib is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in adult patients who are confirmed to possess a rearranged during transfection (RET) gene fusion, as determined by an FDA approved test.⁹ It is also indicated in adult and pediatric patients 12 years of age and older for the treatment of advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and for whom radioactive iodine is not appropriate.¹³ The indication for advanced or metastatic RET fusion-positive thyroid cancer was approved under accelerated approval based on the overall response rate and duration of response, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.¹³

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Advanced ret-fusion non small cell lung cancer		••••••••••••	•••••	••• •••••••••• ••••••• •••• • ••• •••••••••	•••••••
Treatment of	Advanced ret-fusion thyroid cancer		••••••••••••	•••••• •••••••••	••••••••••• •••••••••••••••••• ••••••• •••••••• •••••••	•••••••
Treatment of	Metastatic ret-fusion non small cell lung cancer		••••••••••••	•••••		•••••••
Treatment of	Metastatic ret-fusion thyroid cancer		••••••••••••	•••••• •••••••••	••••••••••• •••••••••••••••••• ••••••• •••••••• •••••••	•••••••

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Pharmacodynamics

Pralsetinib exerts an anti-tumour effect through specific inhibition of the rearranged during transfection (RET) tyrosine kinase, including multiple distinct oncogenic RET fusions, mutated RET kinase domains harbouring gatekeeper mutations, and in RET kinases with a variety of activating single point mutations.^1,2,3,4,9 Due to pralsetinib's high selectivity for RET over other kinases, both in vitro and in vivo,⁵ pralsetinib has been described as having a better safety profile compared to previously used multi-kinase inhibitors.^1,2,3,4 Despite this, pralsetinib use may increase the risk of hypertension, hemorrhagic events, impaired wound healing, hepatotoxicity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.⁹

Mechanism of action

Rearranged during transfection (RET) is a transmembrane receptor tyrosine kinase containing extracellular, transmembrane, and intracellular domains whose activity is required for normal kidney and nervous system development.^6,3 Constitutive RET activation is achieved through chromosomal rearrangements producing 5' fusions of dimerizable domains to the 3' RET tyrosine kinase domain leading to constitutive dimerization and subsequent autophosphorylation; the most common fusions are KIF5B-RET and CCDC6-RET, although more than 35 genes have been reported to fuse with RET.^3,1,7 Constitutive activation leads to increased downstream signalling and is associated with tumour invasion, migration, and proliferation.²

Pralsetinib (formerly referred to as BLU-667) was developed through screening more than 10,000 agnostically designed kinase inhibitors followed by extensive chemical modification to improve its properties. Pralsetinib displays in vitro IC₅₀ values for both WT RET as well as several mutant forms, including CCDC6-RET, in the range of 0.3-0.4 nmol/L, and is 100-fold more selective for RET kinase over 96% of 371 kinases tested.⁵ It is this specific inhibition of RET kinase that is associated with anti-tumour activity and clinical benefit in patients.^5,8,9

Despite increased selectivity for RET over other kinases, pralsetinib has been reported to inhibit DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1-2 at clinically relevant concentrations. The significance of these findings remains uncertain.⁹

Target	Actions	Organism
AProto-oncogene tyrosine-protein kinase receptor Ret	inhibitor	Humans
UEpithelial discoidin domain-containing receptor 1	inhibitor	Humans
UNT-3 growth factor receptor	inhibitor	Humans
UReceptor-type tyrosine-protein kinase FLT3	inhibitor	Humans
UTyrosine-protein kinase JAK1	inhibitor	Humans
UTyrosine-protein kinase JAK2	inhibitor	Humans
UHigh affinity nerve growth factor receptor	inhibitor	Humans
UVascular endothelial growth factor receptor 2	inhibitor	Humans
UPlatelet-derived growth factor receptor beta	inhibitor	Humans
UFibroblast growth factor receptor 1	inhibitor	Humans
UFibroblast growth factor receptor 2	inhibitor	Humans

Absorption

Pralsetinib given at 400 mg once daily resulted in a mean steady-state C_max of 2830 ng/mL (coefficient of variation, CV, 52.5%) and AUC_0-24h of 43900 ng*h/mL (CV 60.2%). The C_max and AUC of pralsetinib increased inconsistently with increasing doses between 60 and 600 mg once daily, with a median T_max across this range of between two and four hours. At 400 mg once daily, pralsetinib reached steady-state plasma concentration by three to five days.⁹

Pralsetinib absorption is affected by food. A single dose of 400 mg given with a high-fat meal (800 to 1000 calories with 50 to 60% of calories coming from fat) increased the mean C_max by 104% (95% CI 65-153%), mean AUC_0-∞ by 122% (95% CI 96-152%), and the median T_max from four to 8.5 hours.⁹

Volume of distribution

Pralsetinib has a mean apparent volume of distribution of 228 L (CV 75%).⁹

Protein binding

Pralsetinib is 97.1% bound to plasma proteins regardless of concentration.⁹

Metabolism

Pralsetinib is metabolized in vitro primarily by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Pralsetinib given as a single oral dose of 310 mg in healthy volunteers led to the detection of metabolites from both oxidation (M453, M531, and M549b) and glucuronidation (M709), although these constituted less than 5% of the detected material.⁹

Route of elimination

Pralsetinib is primarily eliminated through the fecal route (73%, 66% unchanged) with a small amount found in the urine (6%, 4.8% unchanged).⁹

Half-life

Pralsetinib has a plasma elimination half-life of 14.7 ± 6.5 hours following a single dose and 22.2 ± 13.5 hours following multiple doses.⁹

Clearance

Pralsetinib has a mean apparent steady-state oral clearance of 9.1 L/h (CV 60%).⁹

Adverse Effects

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Toxicity

Pralsetinib administered to rats at 20 mg/kg (roughly 2.5-3.6 times the recommended human exposure) resulted in resorption of litters in pregnant female mice in 92% of pregnancies (82% complete resorption); resorption occurred at doses as low as 5 mg/kg (0.3 times the recommended human exposure). Both male and female rats given 10 mg/kg pralsetinib or more had observable degeneration within the testis/ovaries. In 28-day rat and monkey studies, once-daily pralsetinib resulted in histological necrosis at doses 1.1 or more times the recommended human dose and myocardial hemorrhage at doses 2.6 or more times the recommended human dose. Also, pralsetinib induced hyperphosphatemia (rats only, dose 2.4-3.5 times the recommended human dose) and multi-organ mineralization (dose 0.11 or more times the recommended human dose).⁹

Pathways

Not Available

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Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abametapir	The serum concentration of Pralsetinib can be increased when it is combined with Abametapir.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Pralsetinib.
Abrocitinib	The serum concentration of Pralsetinib can be increased when it is combined with Abrocitinib.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Pralsetinib.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Pralsetinib.

Food Interactions

• Take on an empty stomach. Food affects the absorption of pralsetinib. Patients should take pralsetinib either at least one hour before or at least two hours after a meal.

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Gavreto	Capsule	100 mg	Oral	Roche Registration Gmb H	2022-01-17	Not applicable
Gavreto	Capsule	100 mg/1	Oral	Genentech, Inc.	2021-07-01	Not applicable
Gavreto	Capsule	100 mg	Oral	Roche Registration Gmb H	2022-01-17	Not applicable
Gavreto	Capsule	100 mg/1	Oral	Blueprint Medicines Corporation	2020-09-04	2022-04-30
Gavreto	Capsule	100 mg	Oral	Roche Registration Gmb H	2022-01-17	Not applicable

Categories

ATC Codes

L01EX23 — Pralsetinib

• L01EX — Other protein kinase inhibitors
• L01E — PROTEIN KINASE INHIBITORS
• L01 — ANTINEOPLASTIC AGENTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• BCRP/ABCG2 Inhibitors
• BCRP/ABCG2 Substrates
• BSEP/ABCB11 Inhibitors
• Cytochrome P-450 CYP1A2 Substrates
• Cytochrome P-450 CYP2C8 Inducers
• Cytochrome P-450 CYP2C8 Inducers (strength unknown)
• Cytochrome P-450 CYP2C8 Inhibitors
• Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2C9 Inducers
• Cytochrome P-450 CYP2C9 Inducers (strength unknown)
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2D6 Substrates
• Cytochrome P-450 CYP3A Inducers
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inducers
• Cytochrome P-450 CYP3A4 Inducers (strength unknown)
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A5 Inducers
• Cytochrome P-450 CYP3A5 Inducers (strength unknown)
• Cytochrome P-450 CYP3A5 Inhibitors
• Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
• Cytochrome P-450 Enzyme Inducers
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Kinase Inhibitor
• MATE 1 Inhibitors
• MATE 2 Inhibitors
• MATE inhibitors
• OAT1/SLC22A6 inhibitors
• OATP1B1/SLCO1B1 Inhibitors
• OATP1B3 inhibitors
• P-glycoprotein inhibitors
• P-glycoprotein substrates
• Protein Kinase Inhibitors
• Rearranged during Transfection (RET) Inhibitors

Classification

Not classified

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

1WPE73O1WV

CAS number

2097132-94-8

InChI Key

GBLBJPZSROAGMF-RWYJCYHVSA-N

InChI

InChI=1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19-,27+/m0/s1

IUPAC Name

(1s,4s)-N-[(1S)-1-[6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl]ethyl]-1-methoxy-4-{4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}cyclohexane-1-carboxamide

SMILES

CO[C@@]1(CC[C@@H](CC1)C1=NC(NC2=NNC(C)=C2)=CC(C)=N1)C(=O)N[C@@H](C)C1=CC=C(N=C1)N1C=C(F)C=N1

References

Synthesis Reference

Jason D. Brubaker, Joseph L. Kim, Kevin J. Wilson, Douglas Wilson, Lucian V. DiPietro, "Inhibitors of ret." U.S. Patent US20170121312A1, issued July 24, 2018.

General References

1. Russo A, Lopes AR, McCusker MG, Garrigues SG, Ricciardi GR, Arensmeyer KE, Scilla KA, Mehra R, Rolfo C: New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1). Curr Oncol Rep. 2020 Apr 16;22(5):48. doi: 10.1007/s11912-020-00909-8. [Article]
2. Li AY, McCusker MG, Russo A, Scilla KA, Gittens A, Arensmeyer K, Mehra R, Adamo V, Rolfo C: RET fusions in solid tumors. Cancer Treat Rev. 2019 Dec;81:101911. doi: 10.1016/j.ctrv.2019.101911. Epub 2019 Oct 30. [Article]
3. Subbiah V, Yang D, Velcheti V, Drilon A, Meric-Bernstam F: State-of-the-Art Strategies for Targeting RET-Dependent Cancers. J Clin Oncol. 2020 Apr 10;38(11):1209-1221. doi: 10.1200/JCO.19.02551. Epub 2020 Feb 21. [Article]
4. Stinchcombe TE: Current management of RET rearranged non-small cell lung cancer. Ther Adv Med Oncol. 2020 Jul 26;12:1758835920928634. doi: 10.1177/1758835920928634. eCollection 2020. [Article]
5. Subbiah V, Gainor JF, Rahal R, Brubaker JD, Kim JL, Maynard M, Hu W, Cao Q, Sheets MP, Wilson D, Wilson KJ, DiPietro L, Fleming P, Palmer M, Hu MI, Wirth L, Brose MS, Ou SI, Taylor M, Garralda E, Miller S, Wolf B, Lengauer C, Guzi T, Evans EK: Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov. 2018 Jul;8(7):836-849. doi: 10.1158/2159-8290.CD-18-0338. Epub 2018 Apr 15. [Article]
6. Takahashi M, Ritz J, Cooper GM: Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985 Sep;42(2):581-8. doi: 10.1016/0092-8674(85)90115-1. [Article]
7. Qian Y, Chai S, Liang Z, Wang Y, Zhou Y, Xu X, Zhang C, Zhang M, Si J, Huang F, Huang Z, Hong W, Wang K: KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer. Mol Cancer. 2014 Jul 21;13:176. doi: 10.1186/1476-4598-13-176. [Article]
8. Piotrowska Z, Isozaki H, Lennerz JK, Gainor JF, Lennes IT, Zhu VW, Marcoux N, Banwait MK, Digumarthy SR, Su W, Yoda S, Riley AK, Nangia V, Lin JJ, Nagy RJ, Lanman RB, Dias-Santagata D, Mino-Kenudson M, Iafrate AJ, Heist RS, Shaw AT, Evans EK, Clifford C, Ou SI, Wolf B, Hata AN, Sequist LV: Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion. Cancer Discov. 2018 Dec;8(12):1529-1539. doi: 10.1158/2159-8290.CD-18-1022. Epub 2018 Sep 26. [Article]
9. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]
10. Pralsetinib product sheet [Link]
11. Roche News Release: Gavreto for the treatment of NSCLC [Link]
12. FDA Approved Drug Products: GAVRETO (pralsetinib) capsules, for oral use (July 2023) [Link]
13. FDA Approved Drug Products: GAVRETO (pralsetinib) capsules, for oral use (August 2023) [Link]

External Links

ChemSpider

75533827

RxNav

2394936

ChEMBL

CHEMBL4582651

PDBe Ligand

Q4J

Wikipedia

Pralsetinib

PDB Entries

7du9 / 7ju5

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
3	Recruiting	Treatment	Adenocarcinomas / Bronchial Diseases / Bronchogenic Carcinoma / Carcinoma / Head and Neck Neoplasms / Lung Disorder / Lung Neoplasm / Neoplasm / Neoplasms by Histologic Type / Neoplasms by Site / Neoplasms, Embryonal Germ Cell Tumors / Neoplasms, Nerve Tissue / Non-Small Cell Lung Carcinoma / Respiratory Tract Diseases / Respiratory Tract Neoplasms / RET-fusion Non Small Cell Lung Cancer / Thoracic Neoplasms	1
3	Withdrawn	Treatment	Medullary Thyroid Cancer (MTC)	1
2	Active Not Recruiting	Treatment	Advanced Unresectable or Metastatic Solid Malignancy	1
2	Active Not Recruiting	Treatment	Breast Cancer / Gastrointestinal Tract Cancer / Non-Small Cell Lung Cancer (NSCLC) / Other Cancers	1
2	Recruiting	Treatment	Advanced Malignant Neoplasm / Hematological Malignancy / Solid Tumors	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Capsule	Oral	100 mg
Capsule	Oral	100 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US10030005	No	2018-07-24	2036-11-01
US11273160	No	2019-04-03	2039-04-03

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	<0.1 mg/ml	Pralsetinib product sheet

Predicted Properties

Property	Value	Source
logP	3.65	Chemaxon
pKa (Strongest Acidic)	12.45	Chemaxon
pKa (Strongest Basic)	4.13	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	8	Chemaxon
Hydrogen Donor Count	3	Chemaxon
Polar Surface Area	135.53 Å2	Chemaxon
Rotatable Bond Count	8	Chemaxon
Refractivity	146.12 m3·mol-1	Chemaxon
Polarizability	56.66 Å3	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-001i-0002090000-2154411131d142800b8f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0udi-0112390000-ab4bcd61afe14005fc4a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0900-9661210000-85af00e6538de4a2a290
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0udi-0589270000-7549d223055fd1f4caa0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0gca-4220790000-5cc66defd27c0c655d02
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001u-1490210000-84f647420a188a9e5a02

Chromatographic Properties

Collision Cross Sections (CCS)

Not Available

Targets

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Details1. Proto-oncogene tyrosine-protein kinase receptor Ret

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

Curator comments

Inhibition of mutant RET kinase activity is thought to be the main mechanism of action for pralsetinib.

General Function

Transmembrane receptor protein tyrosine kinase activity

Specific Function

Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...

Gene Name

RET

Uniprot ID

P07949

Uniprot Name

Proto-oncogene tyrosine-protein kinase receptor Ret

Molecular Weight

124317.465 Da

References

1. Subbiah V, Gainor JF, Rahal R, Brubaker JD, Kim JL, Maynard M, Hu W, Cao Q, Sheets MP, Wilson D, Wilson KJ, DiPietro L, Fleming P, Palmer M, Hu MI, Wirth L, Brose MS, Ou SI, Taylor M, Garralda E, Miller S, Wolf B, Lengauer C, Guzi T, Evans EK: Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov. 2018 Jul;8(7):836-849. doi: 10.1158/2159-8290.CD-18-0338. Epub 2018 Apr 15. [Article]
2. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details2. Epithelial discoidin domain-containing receptor 1

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Transmembrane receptor protein tyrosine kinase activity

Specific Function

Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, dif...

Gene Name

DDR1

Uniprot ID

Q08345

Uniprot Name

Epithelial discoidin domain-containing receptor 1

Molecular Weight

101126.72 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details3. NT-3 growth factor receptor

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation.

Specific Function

Atp binding

Gene Name

NTRK3

Uniprot ID

Q16288

Uniprot Name

NT-3 growth factor receptor

Molecular Weight

94427.47 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details4. Receptor-type tyrosine-protein kinase FLT3

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Vascular endothelial growth factor-activated receptor activity

Specific Function

Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...

Gene Name

FLT3

Uniprot ID

P36888

Uniprot Name

Receptor-type tyrosine-protein kinase FLT3

Molecular Weight

112902.51 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details5. Tyrosine-protein kinase JAK1

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Ubiquitin protein ligase binding

Specific Function

Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.

Gene Name

JAK1

Uniprot ID

P23458

Uniprot Name

Tyrosine-protein kinase JAK1

Molecular Weight

133275.995 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details6. Tyrosine-protein kinase JAK2

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Sh2 domain binding

Specific Function

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptiv...

Gene Name

JAK2

Uniprot ID

O60674

Uniprot Name

Tyrosine-protein kinase JAK2

Molecular Weight

130672.475 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details7. High affinity nerve growth factor receptor

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Transmembrane receptor protein tyrosine kinase activity

Specific Function

Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympatheti...

Gene Name

NTRK1

Uniprot ID

P04629

Uniprot Name

High affinity nerve growth factor receptor

Molecular Weight

87496.465 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details8. Vascular endothelial growth factor receptor 2

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Vascular endothelial growth factor-activated receptor activity

Specific Function

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...

Gene Name

KDR

Uniprot ID

P35968

Uniprot Name

Vascular endothelial growth factor receptor 2

Molecular Weight

151525.555 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details9. Platelet-derived growth factor receptor beta

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Vascular endothelial growth factor binding

Specific Function

Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...

Gene Name

PDGFRB

Uniprot ID

P09619

Uniprot Name

Platelet-derived growth factor receptor beta

Molecular Weight

123966.895 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details10. Fibroblast growth factor receptor 1

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Protein tyrosine kinase activity

Specific Function

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...

Gene Name

FGFR1

Uniprot ID

P11362

Uniprot Name

Fibroblast growth factor receptor 1

Molecular Weight

91866.935 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

Details11. Fibroblast growth factor receptor 2

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

Curator comments

Pralsetinib is selective for RET over other kinases; detectable inhibition of other kinases at clinically achievable concentrations has been observed but the significance of this inhibition remains unknown.

General Function

Protein tyrosine kinase activity

Specific Function

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...

Gene Name

FGFR2

Uniprot ID

P21802

Uniprot Name

Fibroblast growth factor receptor 2

Molecular Weight

92024.29 Da

References

1. FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules [Link]

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Drug created at September 10, 2020 13:51 / Updated at December 05, 2023 12:31