Mavelertinib | PF-06747775 | CAS#1776112-90-3 | EGFR T790 inhibitor

MedKoo Cat#: 206199 | Name: Mavelertinib

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Mavelertinib, also known as PF-06747775, is an orally available inhibitor of the epidermal growth factor receptor (EGFR) mutant form T790M, with potential antineoplastic activity. EGFR T790M inhibitor PF-06747775 specifically binds to and inhibits EGFR T790M, a secondarily acquired resistance mutation, which prevents EGFR-mediated signaling and leads to cell death in EGFR T790M-expressing tumor cells. Compared to some other EGFR inhibitors, PF-06747775 may have therapeutic benefits in tumors with T790M-mediated drug resistance.

Chemical Structure

Mavelertinib

CAS#1776112-90-3

Theoretical Analysis

MedKoo Cat#: 206199

Name: Mavelertinib

CAS#: 1776112-90-3

Chemical Formula: C18H22FN9O2

Exact Mass: 415.1880

Molecular Weight: 415.43

Elemental Analysis: C, 52.04; H, 5.34; F, 4.57; N, 30.34; O, 7.70

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 285.00	2 Weeks
10mg	USD 485.00	2 Weeks

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Synonym

PF06747775; PF06747775; PF 06747775; PF6747775; PF 6747775; PF6747775; mavelertinib;

IUPAC/Chemical Name

N-((3R,4R)-4-fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidin-3-yl)acrylamide

InChi Key

JYIUNVOCEFIUIU-GHMZBOCLSA-N

InChi Code

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

SMILES Code

C=CC(N[C@@H]1CN(C2=NC(NC3=CN(C)N=C3OC)=C4N=CN(C)C4=N2)C[C@H]1F)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S9G12M19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Mavelertinib is a selective, orally available and irreversible EGFR tyrosine kinase inhibitor (EGFR TKI), with IC50s of 5, 4, 12 and 3 nM for Del, L858R, and double mutants T790M/L858R and T790M/Del, respectively.

In vitro activity:

Herein, this study describes the continued efforts to achieve potency across EGFR oncogenic mutations and improved kinome selectivity, resulting in the discovery of clinical candidate PF-06747775 (21), 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. Reference: J Med Chem. 2017 Apr 13;60(7):3002-3019. https://pubmed.ncbi.nlm.nih.gov/28287730/

In vivo activity:

Mavelertinib, dosed as low as 5 mg/kg of body weight or as high as 50 mg/kg, was efficacious in the acute murine Giardia infection model. These results suggest that mavelertinib merits consideration for repurposing and advancement to giardiasis clinical trials while its analogues are further developed. Reference: Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0001722. https://pubmed.ncbi.nlm.nih.gov/35703552/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.5	114.34

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 415.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Planken S, Behenna DC, Nair SK, Johnson TO, Nagata A, Almaden C, Bailey S, Ballard TE, Bernier L, Cheng H, Cho-Schultz S, Dalvie D, Deal JG, Dinh DM, Edwards MP, Ferre RA, Gajiwala KS, Hemkens M, Kania RS, Kath JC, Matthews J, Murray BW, Niessen S, Orr ST, Pairish M, Sach NW, Shen H, Shi M, Solowiej J, Tran K, Tseng E, Vicini P, Wang Y, Weinrich SL, Zhou R, Zientek M, Liu L, Luo Y, Xin S, Zhang C, Lafontaine J. 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. J Med Chem. 2017 Apr 13;60(7):3002-3019. doi: 10.1021/acs.jmedchem.6b01894. Epub 2017 Mar 29. PMID: 28287730. 2. Michaels SA, Hulverson MA, Whitman GR, Tran LT, Choi R, Fan E, McNamara CW, Love MS, Ojo KK. Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy. Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0001722. doi: 10.1128/aac.00017-22. Epub 2022 Jun 15. PMID: 35703552; PMCID: PMC9295539.

In vitro protocol:

In vivo protocol:

1. Michaels SA, Hulverson MA, Whitman GR, Tran LT, Choi R, Fan E, McNamara CW, Love MS, Ojo KK. Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy. Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0001722. doi: 10.1128/aac.00017-22. Epub 2022 Jun 15. PMID: 35703552; PMCID: PMC9295539.

1: Planken S, Behenna DC, Nair SK, Johnson TO, Nagata A, Almaden C, Bailey S, Ballard TE, Bernier L, Cheng H, Cho-Schultz S, Dalvie D, Deal JG, Dinh DM, Edwards MP, Ferre RA, Gajiwala KS, Hemkens MD, Kania RS, Kath JC, Matthews J, Murray BW, Niessen S, Orr ST, Pairish M, Sach NW, Shen H, Shi M, Solowiej J, Tran K, Tseng E, Vicini P, Wang Y, Weinrich SL, Zhou R, Zientek M, Liu L, Luo Y, Xin S, Zhang C, Lafontaine JA. 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. J Med Chem. 2017 Mar 13. doi: 10.1021/acs.jmedchem.6b01894. [Epub ahead of print] PubMed PMID: 28287730. 2: Wang S, Cang S, Liu D. Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer. J Hematol Oncol. 2016 Apr 12;9:34. doi: 10.1186/s13045-016-0268-z. Review. PubMed PMID: 27071706; PubMed Central PMCID: PMC4830020.