Lorlatinib
Identification
- Summary
Lorlatinib is an anaplastic lymphoma kinase inhibitor used to treat anaplastic lymphoma kinase positive metastatic non small cell lung cancer.
- Brand Names
- Lorbrena
- Generic Name
- Lorlatinib
- DrugBank Accession Number
- DB12130
- Background
Lorlatinib is a third-generation ALK tyrosine kinase inhibitor (TKI) for patients with ALK-positive metastatic non-small cell lung cancer11 which was first approved by the US FDA in November of 2018. It was subsequently approved by the EMA in 2019 for the treatment of select patients with previously treated advanced ALK-positive non-small cell lung cancer, followed by an expanded approval in 2022 to include lorlatinib as a first-line treatment option in advanced ALK-positive NSCLC. 12
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 406.421
Monoisotopic: 406.155352039 - Chemical Formula
- C21H19FN6O2
- Synonyms
- Lorlatinib
- External IDs
- PF 06463922
- PF-06463922
Pharmacology
- Indication
Lorlatinib is indicated for the treatment of adult patients with ALK-positive metastatic non-small cell lung cancer (NSCLC).11 In the EU, it is indicated for the treatment of adult patients with ALK-positive advanced NSCLC not previously treated with an ALK inhibitor, or whose disease has progressed after using either alectinib or ceritinib, or crizotinib and at least one other ALK inhibitor.12
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 Treatment of Advanced non-small cell lung cancer (nsclc) •••••••••••• ••••• ••••••• ••••••••••• ••••• •••••••••• ••• •• ••• ••••••••• ••••••• •••• •••••• Treatment of Advanced non-small cell lung cancer (nsclc) •••••••••••• ••••• ••••••• ••••••••••• ••••• ••••••••• •• ••••••••• ••••••• •••• •••••• Treatment of Advanced non-small cell lung cancer (nsclc) •••••••••••• ••••• ••••••• •••• •••••• Treatment of Metastatic non-small cell lung cancer •••••••••••• ••••• •••••• - 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
Based on data from Study B7461001, exposure-response relationships for Grade 3 or 4 hypercholesterolemia and for any Grade 3 or 4 adverse reaction were observed at steady-state exposures achieved at the recommended dosage, with higher probability of the occurrence of adverse reactions with increasing lorlatinib exposure Label.
In 295 patients who received lorlatinib at the recommended dosage of 100 mg once daily and had an ECG measurement in the same Study B7461001, the maximum mean change from baseline for their PR interval was 16.4 ms (2-sided 90% upper confidence interval [CI] 19.4 ms) Label. Among the 284 patients with PR interval <200 ms at baseline, 14% had PR interval prolongation ≥200 ms after starting use with lorlatinib Label. The prolongation of PR interval occurred in a concentration-dependent manner and atrioventricular block occurred in 1% of patients Label.
Finally, in 275 patients who received lorlatinib at the recommended dosage in the activity-estimating portion of Study B7461001, no large mean increases from baseline in the QTcF interval (i.e., >20 ms) were detected Label.
- Mechanism of action
Non-small cell lung cancer (NSCLC) accounts for up to 85% of lung cancer cases worldwide and remains a particularly difficult to treat condition 10. The gene rearrangement of anaplastic lymphoma kinase (ALK) is a genetic alteration that drives the development of NSCLC in a number of patients 6,7. Ordinarily, ALK is a natural endogenous tyrosine kinase receptor that plays an important role in the development of the brain and elicits activity on various specific neurons in the nervous system 2,5,6.
Subsequnetly, lorlatinib is a kinase inhibitor with in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK Label. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors Label. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well 10,5. The overall antitumor activity of lorlatinib in in-vivo models appears to be dose-dependent and correlated with the inhibition of ALK phosphorylation Label.
Although many ALK-positive metastatic NSCLC patients respond to initial tyrosine kinase therapies, such patients also often experience tumor progression 8. Various clinical trials performed with lorlatinib, however, have demonstrated its utility to effect tumor regression in ALK-positive metastatic NSCLC patients who experience tumor progression despite current use or having already used various first and second-generation tyrosine kinase inhibitors like crizotinib, alectinib, or ceritinib 9.
Target Actions Organism AALK tyrosine kinase receptor inhibitorHumans - Absorption
The median lorlatinib Tmax was 1.2 hours (0.5 to 4 hours) following a single oral 100 mg dose and 2 hours (0.5 to 23 hours) following 100 mg orally once daily at steady state Label.
The mean absolute bioavailability is 81% (90% CI 75.7%, 86.2%) after oral administration compared to intravenous administration Label.
Administration of lorlatinib with a high fat, high-calorie meal (approximately 1000 calories with 150 calories from protein, 250 calories from carbohydrate, and 500 to 600 calories from fat) had no clinically meaningful effect on lorlatinib pharmacokinetics Label.
- Volume of distribution
The mean (CV%) steady-state volume of distribution (Vss) was 305 L (28%) following a single intravenous dose Label.
- Protein binding
In vitro, lorlatinib was 66% bound to plasma proteins at a concentration of 2.4 µM Label. The blood-to-plasma ratio was 0.99 Label.
- Metabolism
In vitro, lorlatinib is metabolized primarily by CYP3A4 and UGT1A4, with minor contribution from CYP2C8, CYP2C19, CYP3A5, and UGT1A3 Label. In plasma, a benzoic acid metabolite (M8) of lorlatinib resulting from the oxidative cleavage of the amide and aromatic ether bonds of lorlatinib accounted for 21% of the circulating radioactivity in a human [14C] mass balance study Label. The oxidative cleavage metabolite, M8, is pharmacologically inactive Label.
- Route of elimination
Following a single oral 100 mg dose of radiolabeled lorlatinib, 48% of the radioactivity was recovered in urine (<1% as unchanged) and 41% in feces (about 9% as unchanged) Label.
- Half-life
The mean plasma half-life (t½) of lorlatinib was 24 hours (40%) after a single oral 100 mg dose of lorlatinib Label.
- Clearance
The mean oral clearance (CL/F) was 11 L/h (35%) following a single oral 100 mg dose and increased to 18 L/h (39%) at steady state, suggesting autoinduction Label.
- Adverse Effects
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- Toxicity
Although there is no formal data available on the use of lorlatinib in pregnant women, based on findings from animal studies and its mechanism of action, it is believed that lorlatinib can cause embryo-fetal harm when administered to a pregnant woman Label.
There are no data on the presence of lorlatinib or its metabolites in either human or animal milk or its effects on the breastfed infant or on milk production Label. Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with lorlatinib and for 7 days after the final dose Label.
Advise female patients of reproductive potential to use effective non-hormonal contraception during treatment with lorlatinib and for at least 6 months after the final dose Label. Advise females of reproductive potential to use a non-hormonal method of contraception, because lorlatinib can render hormonal contraceptives ineffective Label.
Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with lorlatinib and for at least 3 months after the final dose Label.
Based on findings from animal studies, use of lorlatinib may transiently impair male fertility Label.
The safety and effectiveness of lorlatinib in pediatric patients have not been established Label.
Of the 295 patients in Study B7461001 who received 100 mg lorlatinib orally once daily, 18% of patients were aged 65 years or older Label. Although data are limited, no clinically important differences in safety or efficacy were observed between patients aged 65 years or older and younger patients Label.
No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] with AST > ULN or total bilirubin >1 to 1.5 × ULN with any AST) Label. The recommended dose of lorlatinib has not been established for patients with moderate or severe hepatic impairment Label.
No dose adjustment is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] 30 to 89 mL/min estimated by Cockcroft-Gault) Label. The recommended dose of lorlatinib has not been established for patients with severe renal impairment Label.
Carcinogenicity studies have not been conducted with lorlatinib Label. Lorlatinib was aneugenic in an in vitro assay in human lymphoblastoid TK6 cells and positive for micronuclei formation in vivo in the bone marrow of rats. Lorlatinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay Label.
Dedicated fertility studies were not conducted with lorlatinib Label. Findings in male reproductive organs occurred in repeat-dose toxicity studies and included lower testicular, epididymal, and prostate weights; testicular tubular degeneration/atrophy; prostatic atrophy; and/or epididymal inflammation at 15 mg/kg/day and 7 mg/kg/day in rats and dogs, respectively (approximately 8 and 2 times, respectively, the human exposure at the recommended dose of 100 mg based on AUC) Label. The effects on male reproductive organs were reversible Label.
Distended abdomen, skin rash, and increased cholesterol and triglycerides occurred in animals Label. These findings were accompanied by hyperplasia and dilation of the bile ducts in the liver and acinar atrophy of the pancreas in rats at 15 mg/kg/day and in dogs at 2 mg/kg/day (approximately 8 and 0.5 times, respectively, the human exposure at the recommended dose of 100 mg based on AUC) Label. All effects were reversible within the recovery period Label.
- 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 Lorlatinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Lorlatinib can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be decreased when it is combined with Lorlatinib. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Lorlatinib. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Lorlatinib. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of lorlatinib.
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of lorlatinib and may reduce its serum concentration. Co-administration of lorlatinib with St. John's Wort is contraindicated.
- 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.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lorbrena Tablet 100 mg Oral Pfizer Canada Ulc 2019-04-22 Not applicable Canada Lorbrena Tablet, film coated 25 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2018-11-19 Not applicable US Lorbrena Tablet 25 mg Oral Pfizer Canada Ulc 2019-04-22 Not applicable Canada Lorbrena Tablet, film coated 25 mg/1 Oral U.S. Pharmaceuticals 2023-01-03 Not applicable US Lorbrena Tablet, film coated 100 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2018-11-19 Not applicable US
Categories
- ATC Codes
- L01ED05 — Lorlatinib
- Drug Categories
- Amides
- Amines
- Anaplastic lymphoma kinase (ALK) inhibitors
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 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 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Kinase Inhibitor
- Lactams
- MATE 1 Inhibitors
- MATE inhibitors
- OAT3/SLC22A8 Inhibitors
- Organic Cation Transporter 1 Inhibitors
- P-glycoprotein inducers
- Protein Kinase Inhibitors
- Pyridines
- UGT1A3 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Macrolactams
- Sub Class
- Not Available
- Direct Parent
- Macrolactams
- Alternative Parents
- Pyrazolylpyridines / Alkyl aryl ethers / Aminopyridines and derivatives / Aryl fluorides / Benzenoids / Imidolactams / Tertiary carboxylic acid amides / Pyrazoles / Heteroaromatic compounds / Amino acids and derivatives show 8 more
- Substituents
- 3-pyrazolylpyridine / Alkyl aryl ether / Amine / Amino acid or derivatives / Aminopyridine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole show 25 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- OSP71S83EU
- CAS number
- 1454846-35-5
- InChI Key
- IIXWYSCJSQVBQM-LLVKDONJSA-N
- InChI
- InChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1
- IUPAC Name
- (16R)-19-amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetraazatetracyclo[16.3.1.0^{2,6}.0^{10,15}]docosa-1(22),2,5,10(15),11,13,18,20-octaene-3-carbonitrile
- SMILES
- C[C@H]1OC2=C(N)N=CC(=C2)C2=C(C#N)N(C)N=C2CN(C)C(=O)C2=C1C=C(F)C=C2
References
- Synthesis Reference
Johnson TW, Richardson PF, Bailey S, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014;57(11):4720-44.
- General References
- Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ: Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. doi: 10.1016/S1470-2045(17)30680-0. Epub 2017 Oct 23. [Article]
- Authors unspecified: Lorlatinib in NSCLC: Robust Efficacy Seen. Cancer Discov. 2017 Dec;7(12):1360-1361. doi: 10.1158/2159-8290.CD-NB2017-153. Epub 2017 Nov 3. [Article]
- Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng YL, Liu W, Dardaei L, Frias RL, Schultz KR, Logan J, James LP, Smeal T, Timofeevski S, Katayama R, Iafrate AJ, Le L, McTigue M, Getz G, Johnson TW, Engelman JA: Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F. N Engl J Med. 2016 Jan 7;374(1):54-61. doi: 10.1056/NEJMoa1508887. Epub 2015 Dec 23. [Article]
- Authors unspecified: Lorlatinib Is Active in Drug-Resistant NSCLC. Cancer Discov. 2016 Aug;6(8):OF1. doi: 10.1158/2159-8290.CD-NB2016-087. Epub 2016 Jul 8. [Article]
- Collier TL, Maresca KP, Normandin MD, Richardson P, McCarthy TJ, Liang SH, Waterhouse RN, Vasdev N: Brain Penetration of the ROS1/ALK Inhibitor Lorlatinib Confirmed by PET. Mol Imaging. 2017 Jan-Dec;16:1536012117736669. doi: 10.1177/1536012117736669. [Article]
- Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G: The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008 Jan;8(1):11-23. doi: 10.1038/nrc2291. [Article]
- Guerin A, Sasane M, Zhang J, Macalalad AR, Galebach P, Jarvis J, Kageleiry A, Culver K, Wu EQ, Wakelee H: ALK rearrangement testing and treatment patterns for patients with ALK-positive non-small cell lung cancer. Cancer Epidemiol. 2015 Jun;39(3):307-12. doi: 10.1016/j.canep.2015.04.005. Epub 2015 Apr 23. [Article]
- Lin JJ, Riely GJ, Shaw AT: Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov. 2017 Feb;7(2):137-155. doi: 10.1158/2159-8290.CD-16-1123. Epub 2017 Jan 25. [Article]
- Waqar SN, Morgensztern D: Lorlatinib: a new-generation drug for ALK-positive NSCLC. Lancet Oncol. 2018 Dec;19(12):1555-1557. doi: 10.1016/S1470-2045(18)30789-7. Epub 2018 Nov 6. [Article]
- Drugs.com: FDA Approves Lorbrena [Link]
- FDA Approved Drug Products: Lorbrena (lorlatinib) tablets for oral use [Link]
- EMA Summary of Product Characteristics: Lorviqua (lorlatinib) film-coated tablets for oral use [Link]
- External Links
- PubChem Compound
- 71731823
- PubChem Substance
- 347828429
- ChemSpider
- 32813339
- BindingDB
- 50018830
- 2103164
- ChEBI
- 143117
- ChEMBL
- CHEMBL3286830
- ZINC
- ZINC000098208524
- PDBe Ligand
- 5P8
- Wikipedia
- Lorlatinib
- PDB Entries
- 4cli / 4clj / 4uxl / 5a9u / 5aa8 / 5aa9
- MSDS
- Download (22.3 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 4 Active Not Recruiting Treatment Carcinoma / Non Small Cell Lung 1 4 Completed Treatment Advanced Non-Small Cell Lung Cancer (NSCLC) 1 4 Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1 3 Active Not Recruiting Treatment Ganglioneuroblastoma / Neuroblastoma (NB) 1 3 Active Not Recruiting Treatment Non-Small Cell Lung Carcinoma 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 25 mg/1 Tablet, coated Oral 100 mg Tablet, film coated Oral 100 mg Tablet, coated Oral 25 mg Tablet, film coated Oral 25 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8680111 No 2014-03-25 2033-03-05 US US10420749 No 2019-09-24 2036-07-27 US US11020376 No 2021-06-01 2036-07-27 US US11299500 No 2018-10-04 2038-10-04 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.108 mg/mL ALOGPS logP 2.01 ALOGPS logP 1.63 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 19.7 Chemaxon pKa (Strongest Basic) 5.71 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 110.06 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 121.17 m3·mol-1 Chemaxon Polarizability 40.42 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 GC-MS Spectrum - GC-MS Predicted GC-MS splash10-002f-0009000000-e537208c5bf520bb96f4 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0001900000-4cb45473dad0835a5c79 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0003900000-f3686dca913cf2ebc591 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0009800000-268de9b6ea6bd3de4382 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-05n0-6009500000-dc6a18773308ed1d281c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03k9-0009000000-ea2b848c1a128e2c06b2 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0229-0009000000-504bac2c8ae66a8bb759 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]- 194.90593 predictedDeepCCS 1.0 (2019) [M+H]+ 197.3015 predictedDeepCCS 1.0 (2019) [M+Na]+ 203.25719 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
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis a...
- Gene Name
- ALK
- Uniprot ID
- Q9UM73
- Uniprot Name
- ALK tyrosine kinase receptor
- Molecular Weight
- 176440.535 Da
Enzymes
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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...
Components:
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- 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
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- 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
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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. Isoform 2 lacks transferase activity but acts as a negative reg...
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1-3
- Molecular Weight
- 60337.835 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- 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
- DailyMed Label: LORBRENA (lorlatinib) tablets, for oral use [Link]
Drug created at October 20, 2016 21:24 / Updated at February 20, 2024 23:54