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

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAdvanced non-small cell lung cancer (nsclc)•••••••••••••••••••••••• ••••••••••• ••••• •••••••••• ••• •• ••• •••••••••••••••• •••• ••••••
Treatment ofAdvanced non-small cell lung cancer (nsclc)•••••••••••••••••••••••• ••••••••••• ••••• ••••••••• •• •••••••••••••••• •••• ••••••
Treatment ofAdvanced non-small cell lung cancer (nsclc)•••••••••••••••••••••••• •••• ••••••
Treatment ofMetastatic non-small cell lung cancer•••••••••••••••••••••••
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
AALK tyrosine kinase receptor
inhibitor
Humans
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.
DrugInteraction
AbametapirThe serum concentration of Lorlatinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Lorlatinib can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Lorlatinib.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Lorlatinib.
AcenocoumarolThe 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

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LorbrenaTablet100 mgOralPfizer Canada Ulc2019-04-22Not applicableCanada flag
LorbrenaTablet, film coated25 mg/1OralPfizer Laboratories Div Pfizer Inc2018-11-19Not applicableUS flag
LorbrenaTablet25 mgOralPfizer Canada Ulc2019-04-22Not applicableCanada flag
LorbrenaTablet, film coated25 mg/1OralU.S. Pharmaceuticals2023-01-03Not applicableUS flag
LorbrenaTablet, film coated100 mg/1OralPfizer Laboratories Div Pfizer Inc2018-11-19Not applicableUS flag

Categories

ATC Codes
L01ED05 — Lorlatinib
Drug Categories
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. Drugs.com: FDA Approves Lorbrena [Link]
  11. FDA Approved Drug Products: Lorbrena (lorlatinib) tablets for oral use [Link]
  12. EMA Summary of Product Characteristics: Lorviqua (lorlatinib) film-coated tablets for oral use [Link]
PubChem Compound
71731823
PubChem Substance
347828429
ChemSpider
32813339
BindingDB
50018830
RxNav
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);">
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentCarcinoma / Non Small Cell Lung1
4CompletedTreatmentAdvanced Non-Small Cell Lung Cancer (NSCLC)1
4RecruitingTreatmentNon-Small Cell Lung Cancer (NSCLC)1
3Active Not RecruitingTreatmentGanglioneuroblastoma / Neuroblastoma (NB)1
3Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral100 mg
TabletOral25 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, coatedOral100 mg
Tablet, film coatedOral100 mg
Tablet, coatedOral25 mg
Tablet, film coatedOral25 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8680111No2014-03-252033-03-05US flag
US10420749No2019-09-242036-07-27US flag
US11020376No2021-06-012036-07-27US flag
US11299500No2018-10-042038-10-04US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.108 mg/mLALOGPS
logP2.01ALOGPS
logP1.63Chemaxon
logS-3.6ALOGPS
pKa (Strongest Acidic)19.7Chemaxon
pKa (Strongest Basic)5.71Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area110.06 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity121.17 m3·mol-1Chemaxon
Polarizability40.42 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-002f-0009000000-e537208c5bf520bb96f4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0001900000-4cb45473dad0835a5c79
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0003900000-f3686dca913cf2ebc591
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009800000-268de9b6ea6bd3de4382
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-05n0-6009500000-dc6a18773308ed1d281c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03k9-0009000000-ea2b848c1a128e2c06b2
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0229-0009000000-504bac2c8ae66a8bb759
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-194.90593
predicted
DeepCCS 1.0 (2019)
[M+H]+197.3015
predicted
DeepCCS 1.0 (2019)
[M+Na]+203.25719
predicted
DeepCCS 1.0 (2019)

Targets

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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
Substrate
Inhibitor
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
Substrate
Inhibitor
Inducer
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
  1. DailyMed Label: LORBRENA (lorlatinib) tablets, for oral use [Link]

Drug created at October 20, 2016 21:24 / Updated at February 20, 2024 23:54