Glasdegib
Identification
- Summary
Glasdegib is a sonic hedgehog receptor inhibitor used to treat newly diagnosed acute myeloid leukemia in patients over 75 years who cannot receive intense chemotherapy.
- Brand Names
- Daurismo
- Generic Name
- Glasdegib
- DrugBank Accession Number
- DB11978
- Background
Glasdegib, also known as PF-04449913, is a small-molecule hedgehog signaling inhibitor selected under the group of benzimidazoles. In early research, benzimidazoles attracted large interest as they represented a class of inhibitors with low molecular weight, potent inhibitory activity, and lacking unstable functionality.1 The great lipophilicity of this group of compounds brought interest to further modification. This analysis concluded that the presence of p-cyano ureas presented good physicochemical and pharmacokinetic properties from which glasdegib was developed.1
Glasdegib was developed by Pfizer Inc and approved on November 21, 2018 by the FDA for the treatment of Acute Myeloid Leukemia (AML).11 Glasdegib targets cancerous cells by inhibiting the sonic hedgehog receptor smoothened (SMO), a transmembrane protein involved in the Hedgehog (Hh) signaling cascade.5 Aberrant of Hh signaling is one of the main pathophysiologies of AML, with observed overexpression or constitutive activation of SMO.6,7 Although the efficacy of glasdegib monotherapy is limited, the landmark Phase 2 Bright AML 1003 trial showed a superior overall survival and complete response when glasdegib is combined with low dose cytarabine. Currently, the current gold standard of AML in older patients is still venetoclax with hypomethylation agents, new clinical combinations of glasdegib are being tested in hope of replacing venetoclax due to glasdegib's more favorable side effects profile.5
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 374.448
Monoisotopic: 374.185509352 - Chemical Formula
- C21H22N6O
- Synonyms
- Glasdegib
- External IDs
- PF 04449913
- PF-04449913
- PF-4449913
Pharmacology
- Indication
Glasdegib, in combination with cytarabine, is indicated for the treatment of newly diagnosed acute myeloid leukemia in adult patients who are over 75 years old or that have co-morbidities that preclude intensive induction chemotherapy.9
Acute myeloid leukemia is characterized by abnormal production of myeloblasts, red cells, or platelets. It is considered a cancer of blood and bone marrow and it is the most common type of acute leukemia in adults.10
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Acute myeloid leukemia Regimen in combination with: Cytarabine (DB00987) •••••••••••• •••••• ••••••• ••••••• •••• •••••• Used in combination to treat Acute myeloid leukemia (aml) Regimen in combination with: Cytarabine (DB00987) •••••••••••• ••••• ••••••••••••• •••• •••••••• ••••••••• •••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
In preclinical studies, glasdegib achieved a significant reduction in leukemic stem cell burden in xenograft models and a reduction in cell population expressing leukemic stem cell markers.2
In clinical trials, glasdegib demonstrated a marked downregulation of more than 80% of the expression of glioma-associated transcriptional regulator GL11 in skin. In this same study 8% of the studied individuals with acute myeloid leukemia achieved morphological complete remission while 31% achieved stable disease state.2
The latest clinical trial proved glasdegib to generate an overall survival of 8.3 months which was almost double to what has been observed in patients under low-dose cytarabine treatment. As well, there have been reports of dose-dependent QTc prolongation in patients administered with glasdegib.9
- Mechanism of action
Glasdegib is a potent and selective inhibitor of the hedgehog signaling pathway that acts by binding to the smoothened (SMO) receptor.1
The hedgehog signaling pathway is involved in maintenance of neural and skin stem cells. In this pathway, the binding of specific ligands to the transmembrane receptor patched (PTCH1) allows the activation of the transcriptional regulators GL11, GL12 and modulation of the gene expression through SMO-mediated signaling. The aberrant activation of the hedgehog pathway is thought to be implicated in the pathogenesis of chronic myeloid leukemia, medulloblastoma and basal cell carcinoma due to the hyperproliferative state that a modification on this pathway will produce.3
Target Actions Organism ASmoothened homolog inhibitorHumans - Absorption
Glasdegib presents a dose-proportional pharmacokinetic profile which is observed by the presence of a broad dose-proportional maximum plasma concentration. In this study and on a dose of 50 mg, the median time to reach a maximum concentration of 321 ng/ml was of 4 hours with an AUC of 9587 ng.h/ml.2 The oral bioavailability of glasdegib is reported to be of 55%.1
In a multiple dose study of 50 mg, the Cmax, tmax and AUC was reported to be 542 ng/ml, 4 h and 9310 ng.h/ml respectively. In this same study, the average concentration at a steady state was of 388 ng/ml.2
The absorption rates of glasdegib can be modified by the concomitant consumption of a high-fat, high-calorie meal.Label
- Volume of distribution
Glasdegib reported volume of distribution in a dose of 50 mg is 225 L.2 The geometric mean (%CV) apparent volume of distribution (Vz/F) was 188 L (20%) in patients with hematologic malignancies.12
- Protein binding
Glasdegib is reported to be 91% protein bounded which is explained due to its high lipophilic profile.8
- Metabolism
After oral administration, glasdegib was primarily metabolized by CYP3A4 with minor contributions of CYP2C8 and UGT1A9. The amount of unchanged glasdegib in plasma accounts only for 69% of the administered dose.4
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- Route of elimination
From a single oral dose of 100 mg radiolabeled glasdegib, 49% is eliminated in the urine from which 17% is excreted as the unchanged form while 42% is eliminated in feces where 20% represents the unchanged form.4,12
- Half-life
The reported half-life of glasdegib is of 17.4 hours.8
- Clearance
The clearance rate of 50 mg of glasdegib is reported to be of 5.22 L/h.2 The geometric mean (%CV) apparent clearance of 6.45 L/h (25%) following 100 mg once daily dosing in patients with hematologic malignancies.12
- Adverse Effects
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- Toxicity
Based on its mechanism of action and findings in animal embryo-fetal developmental toxicity studies, glasdegib can cause fetal harm when administered to a pregnant woman. There are no clinical data on the use of glasdegib in pregnant women to inform of a drug-associated risk of major birth defects and miscarriage. Glasdegib is not recommended for use during pregnancy. Conduct pregnancy testing in female patients of reproductive potential prior to initiating treatment with glasdegib. Report pregnancy exposures to Pfizer at 1-800-438-1985.12
In animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of glasdegib during organogenesis at maternal exposures that were less than the human exposure at the recommended dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus.12
Carcinogenicity studies have not been performed with glasdegib. Glasdegib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro chromosome aberration assay in human lymphocytes. Glasdegib was not clastogenic or aneugenic in the rat micronucleus assay.12
Based on nonclinical safety findings, glasdegib has the potential to impair reproductive function in males. Men should seek advice on effective fertility preservation before treatment. In repeat-dose toxicity studies in rats, findings observed in the male reproductive tract included adverse testicular changes with glasdegib at doses ≥50 mg/kg/day and consisted of minimal to severe hypospermatogenesis characterized by partial to complete loss of spermatogonia, spermatocytes and spermatids and testicular degeneration. Hypospermatogenesis did not recover whereas testicular degeneration did recover. The dose at which testicular effects were observed in male rats was identified as 50 mg/kg/day with corresponding systemic exposures that were approximately 6.6 times (based on AUC) those associated with the observed human exposure at the 100 mg once daily dose.
There is no specific antidote for DAURISMO. Management of DAURISMO overdose should include symptomatic treatment and ECG monitoring. Glasdegib has been administered in clinical studies up to a dose of 640 mg/day. At the highest dosage, the adverse reactions that were dose-limiting were nausea, vomiting, dehydration, hypotension, fatigue, and dizziness.12
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Glasdegib can be increased when it is combined with Abametapir. Abatacept The metabolism of Glasdegib can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Glasdegib. Abiraterone The metabolism of Glasdegib can be decreased when combined with Abiraterone. Abrocitinib The serum concentration of Glasdegib can be increased when it is combined with Abrocitinib. - Food Interactions
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of glasdegib.
- Take at the same time every day.
- Take with or without food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Glasdegib hydrochloride 4Y7R3PBO4V 1095173-64-0 OCHAAZGYSAHXOF-LJLRIERRSA-N Glasdegib maleate TH2EV99S4Z 2030410-25-2 VJCVKWFBWAVYOC-UIXXXISESA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Daurismo Tablet, film coated 100 mg Oral Pfizer Europe Ma Eeig 2021-03-16 Not applicable EU Daurismo Tablet, film coated 25 mg Oral Pfizer Europe Ma Eeig 2021-03-16 Not applicable EU Daurismo Tablet, film coated 100 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2018-12-10 Not applicable US Daurismo Tablet, film coated 100 mg Oral Pfizer Europe Ma Eeig 2021-03-16 Not applicable EU Daurismo Tablet 100 mg Oral Pfizer Canada Ulc 2020-08-10 Not applicable Canada
Categories
- ATC Codes
- L01XJ03 — Glasdegib
- Drug Categories
- Amides
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Benzene Derivatives
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Hedgehog Pathway Inhibitor
- Hedgehog pathway inhibitors
- Heterocyclic Compounds, Fused-Ring
- Highest Risk QTc-Prolonging Agents
- MATE 1 Inhibitors
- MATE 2 Inhibitors
- MATE inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- QTc Prolonging Agents
- Smoothened Receptor Antagonists
- UGT1A9 Substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n-phenylureas. These are compounds containing a N-phenylurea moiety, which is structurally characterized by a phenyl group linked to one nitrogen atom of a urea group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- N-phenylureas
- Direct Parent
- N-phenylureas
- Alternative Parents
- Benzimidazoles / Benzonitriles / Aralkylamines / Piperidines / Imidazoles / Heteroaromatic compounds / Ureas / Trialkylamines / Nitriles / Azacyclic compounds show 3 more
- Substituents
- Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzimidazole / Benzonitrile / Carbonitrile / Carbonyl group / Cyanide show 15 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- K673DMO5H9
- CAS number
- 1095173-27-5
- InChI Key
- SFNSLLSYNZWZQG-VQIMIIECSA-N
- InChI
- InChI=1S/C21H22N6O/c1-27-11-10-16(24-21(28)23-15-8-6-14(13-22)7-9-15)12-19(27)20-25-17-4-2-3-5-18(17)26-20/h2-9,16,19H,10-12H2,1H3,(H,25,26)(H2,23,24,28)/t16-,19-/m1/s1
- IUPAC Name
- 1-[(2R,4R)-2-(1H-1,3-benzodiazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea
- SMILES
- CN1CC[C@H](C[C@@H]1C1=NC2=CC=CC=C2N1)NC(=O)NC1=CC=C(C=C1)C#N
References
- Synthesis Reference
Munchhof MJ, Li Q, Shavnya A, et al. Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened. ACS Med Chem Lett. 2012;3(2):106-11.
- General References
- Munchhof MJ, Li Q, Shavnya A, Borzillo GV, Boyden TL, Jones CS, LaGreca SD, Martinez-Alsina L, Patel N, Pelletier K, Reiter LA, Robbins MD, Tkalcevic GT: Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened. ACS Med Chem Lett. 2011 Dec 21;3(2):106-11. doi: 10.1021/ml2002423. eCollection 2012 Feb 9. [Article]
- Minami Y, Minami H, Miyamoto T, Yoshimoto G, Kobayashi Y, Munakata W, Onishi Y, Kobayashi M, Ikuta M, Chan G, Woolfson A, Ono C, Shaik MN, Fujii Y, Zheng X, Naoe T: Phase I study of glasdegib (PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies. Cancer Sci. 2017 Aug;108(8):1628-1633. doi: 10.1111/cas.13285. Epub 2017 Jun 19. [Article]
- Irvine DA, Copland M: Targeting hedgehog in hematologic malignancy. Blood. 2012 Mar 8;119(10):2196-204. doi: 10.1182/blood-2011-10-383752. Epub 2012 Jan 5. [Article]
- Lam JL, Vaz A, Hee B, Liang Y, Yang X, Shaik MN: Metabolism, excretion and pharmacokinetics of [(14)C]glasdegib (PF-04449913) in healthy volunteers following oral administration. Xenobiotica. 2017 Dec;47(12):1064-1076. doi: 10.1080/00498254.2016.1261307. Epub 2017 Jan 3. [Article]
- Iyer SG, Stanchina M, Bradley TJ, Watts J: Profile of Glasdegib for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML): Evidence to Date. Cancer Manag Res. 2022 Aug 1;14:2267-2272. doi: 10.2147/CMAR.S195723. eCollection 2022. [Article]
- Jamieson C, Martinelli G, Papayannidis C, Cortes JE: Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia. Blood Cancer Discov. 2020 Aug 11;1(2):134-145. doi: 10.1158/2643-3230.BCD-20-0007. eCollection 2020 Sep. [Article]
- Terao T, Minami Y: Targeting Hedgehog (Hh) Pathway for the Acute Myeloid Leukemia Treatment. Cells. 2019 Apr 3;8(4):312. doi: 10.3390/cells8040312. [Article]
- Bethesda (2006). Drugs and Lactation Database. National Library of Medicine.
- FDA news [Link]
- NIH [Link]
- FDA Approved Drug Products: Daurismo (glasdegib) oral tablets [Link]
- FDA Approved Drug Products: Daurismo (glasdegib) oral tablets (March 2023) [Link]
- EMA Assessment Report: Daurismo International non-proprietary name glasdegib [Link]
- Pfizer Glasdegib product information [File]
- External Links
- PubChem Compound
- 25166913
- PubChem Substance
- 347828300
- ChemSpider
- 28518072
- BindingDB
- 50385635
- 2105845
- ChEBI
- 145428
- ChEMBL
- CHEMBL2043437
- ZINC
- ZINC000068251434
- Wikipedia
- Glasdegib
- FDA label
- Download (572 KB)
- MSDS
- Download (24.6 KB)
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 Completed Treatment Acute Myeloid Leukemia 1 3 Completed Treatment Acute Myeloid Leukemia / Chronic Myelomonocytic Leukemia / Myelodysplastic Syndrome 1 3 Recruiting Health Services Research Soft Tissue Sarcoma 1 3 Recruiting Treatment Acute Myeloid Leukemia 1 3 Terminated Treatment Acute Myeloid Leukemia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet Oral 25 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 100 MG Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 25 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8431597 No 2013-04-30 2028-06-29 US US8148401 No 2012-04-03 2031-01-30 US US10414748 No 2019-09-17 2036-04-13 US US11168066 No 2021-11-09 2036-04-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 0.02 mg/ml (in the form of di-HCl monohydrate salt) Munchhof M., et al. (2011). ACS Med Chem Lett. logP 2.28 Munchhof M., et al. (2011). ACS Med Chem Lett. Caco2 permeability 0.00000598 Munchhof M., et al. (2011). ACS Med Chem Lett. pKa 6 Munchhof M., et al. (2011). ACS Med Chem Lett. - Predicted Properties
Property Value Source Water Solubility 0.0469 mg/mL ALOGPS logP 2.68 ALOGPS logP 2.28 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 11.39 Chemaxon pKa (Strongest Basic) 6.67 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 96.84 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 108.26 m3·mol-1 Chemaxon Polarizability 40.73 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No 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 splash10-004i-0049000000-95adfc803c1d43ca30ba Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0395000000-e2bf38ac0737cad4bda1 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0189000000-56dfc6f45f475567ee71 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-002f-9581000000-f9bde29ab07cf8da4667 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05ox-4938000000-f6d5c9edfc7d0b28d876 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-2922000000-38b506603028dba063be Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 179.29291 predictedDeepCCS 1.0 (2019) [M+H]+ 181.68848 predictedDeepCCS 1.0 (2019) [M+Na]+ 188.2357 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Wnt-protein binding
- Specific Function
- G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought t...
- Gene Name
- SMO
- Uniprot ID
- Q99835
- Uniprot Name
- Smoothened homolog
- Molecular Weight
- 86395.95 Da
References
- Munchhof MJ, Li Q, Shavnya A, Borzillo GV, Boyden TL, Jones CS, LaGreca SD, Martinez-Alsina L, Patel N, Pelletier K, Reiter LA, Robbins MD, Tkalcevic GT: Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened. ACS Med Chem Lett. 2011 Dec 21;3(2):106-11. doi: 10.1021/ml2002423. eCollection 2012 Feb 9. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Lam JL, Vaz A, Hee B, Liang Y, Yang X, Shaik MN: Metabolism, excretion and pharmacokinetics of [(14)C]glasdegib (PF-04449913) in healthy volunteers following oral administration. Xenobiotica. 2017 Dec;47(12):1064-1076. doi: 10.1080/00498254.2016.1261307. Epub 2017 Jan 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Daurismo (glasdegib) oral tablets (March 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1-9
- Molecular Weight
- 59940.495 Da
References
- Lam JL, Vaz A, Hee B, Liang Y, Yang X, Shaik MN: Metabolism, excretion and pharmacokinetics of [(14)C]glasdegib (PF-04449913) in healthy volunteers following oral administration. Xenobiotica. 2017 Dec;47(12):1064-1076. doi: 10.1080/00498254.2016.1261307. Epub 2017 Jan 3. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- EMA Assessment Report: Daurismo International non-proprietary name glasdegib [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Components:
References
- EMA Assessment Report: Daurismo International non-proprietary name glasdegib [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: Daurismo (glasdegib) oral tablets (March 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: Daurismo (glasdegib) oral tablets (March 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Monovalent cation:proton antiporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- FDA Approved Drug Products: Daurismo (glasdegib) oral tablets (March 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Drug transmembrane transporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- FDA Approved Drug Products: Daurismo (glasdegib) oral tablets (March 2023) [Link]
Drug created at October 20, 2016 21:07 / Updated at February 20, 2024 23:54