MAVELERTINIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H22FN9O2
Molecular Weight	415.4248
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=NN(C)C=C1NC2=NC(=NC3=C2N=CN3C)N4C[C@@H](F)[C@@H](C4)NC(=O)C=C

InChI

InChIKey=JYIUNVOCEFIUIU-GHMZBOCLSA-N

InChI=1S/C18H22FN9O2/c1-5-13(29)21-11-8-28(6-10(11)19)18-23-15(14-16(24-18)26(2)9-20-14)22-12-7-27(3)25-17(12)30-4/h5,7,9-11H,1,6,8H2,2-4H3,(H,21,29)(H,22,23,24)/t10-,11-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C18H22FN9O2
Molecular Weight	415.4248
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28287730

PF-06747775 is an irreversible pyrrolopyrimidine inhibitor of epidermal growth factor receptor (EGFR) T790M mutants which provides potent EGFR activity against the four common mutants (exon 19 deletion (Del), L858R, and double mutants T790M/L858R and T790M/Del), selectivity over wild-type EGFR, and desirable ADME properties. The third-generation class of EGFR tyrosine kinase inhibitors PF-06747775 is a clinical candidate drug for treatment of non-small-cell lung cancer (NSCLC) driven by mutant EGFR.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Epidermal growth factor receptor 46 Target ID: P00533\|\|\|Q9GZX1 Gene ID: 1956.0 Gene Symbol: EGFR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28287730	Inhibitor 8297		3.0 nM [IC50]
Epidermal growth factor receptor erbB1 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28287730	Inhibitor 8297		307.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT02349633	Primary		Phase II 1132	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28287730	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PF-06747775 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
22% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28287730	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PF-06747775 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/results/NCT02349633	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: Non-small cell lung cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://clinicaltrials.gov/ct2/show/results/NCT02349633	Other AEs: Dermatitis acneiform, Lacrimation increased... Other AEs: Dermatitis acneiform (25%) Lacrimation increased (25%) Paronychia (50%) Vision blurred (25%) Migraine (25%) Rash pustular (25%) Ileus (serious, 25%) sinusitis (25%) Abdominal pain (50%) Diarrhoea (100%) Pyrexia (serious, 25%) Dry skin (25%) Cough (25%) Nausea (25%) Blood creatinine increased (50%) Stomatitis (25%) Pneumonia (serious, 25%) Dehydration (serious, 25%) Blood urea increased (25%) Vomiting (25%) Hyponatraemia (serious, 25%) Ingrowing nail (25%) Weight decreased (25%) Dyspnoea (serious, 25%) Mucosal inflammation (50%) Anaemia (serious, 25%) Dry eye (25%) Malaise (25%) Decreased appetite (25%) Pruritus (25%) Conjunctivitis (25%) Dyspnoea (25%) Hypokalaemi (50%) Epistaxis (25%) Headache (50%) Flushing (25%) Rhinorrhoea (25%) rash (50%) Sources: https://clinicaltrials.gov/ct2/show/results/NCT02349633

AEs

PubMed

Title	Date	PubMed
Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer.	2016 Apr 12	27071706
Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR.	2017 Apr 13	28287730
Recent updates on third generation EGFR inhibitors and emergence of fourth generation EGFR inhibitors to combat C797S resistance.	2017 Dec 15	28526474

Patents

Sample Use Guides

In Vivo Use Guide

PF-06747775 administered as continuous daily dosing in 21-day cycles. The starting dose of PF-06747775 25 mg daily.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:32:38 UTC 2023` Edited by `admin` on `Sat Dec 16 09:32:38 UTC 2023`
Record UNII	YXX2180047
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MAVELERTINIB

Official Name

English

N-((3R,4R)-4-FLUORO-1-(6-((3-METHOXY-1-METHYL-PYRAZOL-4-YL)AMINO)-9-METHYL-PURIN-2-YL)PYRROLIDIN-3-YL)PROP-2-ENAMIDE

Systematic Name

English

PF-06747775

Common Name

English

2-PROPENAMIDE, N-((3R,4R)-4-FLUORO-1-(6-((3-METHOXY-1-METHYL-1H-PYRAZOL-4-YL)AMINO)-9-METHYL-9H-PURIN-2-YL)-3-PYRROLIDINYL)-

Systematic Name

English

mavelertinib [INN]

Common Name

English

EGFR T790M INHIBITOR PF-06747775

Common Name

English

Mavelertinib [WHO-DD]

Common Name

English

MAVELERTINIB [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825