Mobocertinib free base| CAS# 1847461-43-1 | Tyrosine Kinase Inhibitor

MedKoo Cat#: 558746 | Name: Mobocertinib free base

Description:

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

Mobocertinib, also known as TAK-788 and AP32788, is an investigational TKI with potent, selective preclinical activity against activating EGFR and HER2 mutations, including exon 20 insertions. TAK-788 exhibits antitumor activity in pts with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs.

Chemical Structure

Mobocertinib free base

CAS#1847461-43-1 (free base)

Theoretical Analysis

MedKoo Cat#: 558746

Name: Mobocertinib free base

CAS#: 1847461-43-1 (free base)

Chemical Formula: C32H39N7O4

Exact Mass: 585.3064

Molecular Weight: 585.71

Elemental Analysis: C, 65.62; H, 6.71; N, 16.74; O, 10.93

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 425.00	Ready to ship
200mg	USD 685.00	Ready to ship
500mg	USD 1,450.00	Ready to ship
1g	USD 2,450.00	Ready to ship
2g	USD 4,250.00	Ready to ship

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Related CAS #

2389149-85-1 (mesylate) 1847461-43-1 (free base) 2389149-74-8 (succinate) 2389149-76-0 (HBr) 2389149-79-3 (HCl) 2389149-81-7 (sulfate) 2389149-83-9 (tosylate) 2389149-87-3 (oxalate) 2389149-89-5 (fumarate)

Synonym

Mobocertinib; TAK-788; TAK 788; TAK788; AP32788; AP-32788; AP 32788;Mobocertinib free base

IUPAC/Chemical Name

propan-2-yl 2-[4-{[2-(dimethylamino)ethyl](methyl)amino}-2-methoxy-5-(prop-2-enamido)anilino]-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate

InChi Key

AZSRSNUQCUDCGG-UHFFFAOYSA-N

InChi Code

InChI=1S/C32H39N7O4/c1-9-29(40)34-24-16-25(28(42-8)17-27(24)38(6)15-14-37(4)5)35-32-33-18-22(31(41)43-20(2)3)30(36-32)23-19-39(7)26-13-11-10-12-21(23)26/h9-13,16-20H,1,14-15H2,2-8H3,(H,34,40)(H,33,35,36)

SMILES Code

O=C(C1=CN=C(NC2=CC(NC(C=C)=O)=C(N(CCN(C)C)C)C=C2OC)N=C1C3=CN(C)C4=C3C=CC=C4)OC(C)C

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

Shelf Life

>3 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#A20T09K27

QC Data

View QC data: current batch, Lot#A20T09K27

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Mobocertinib (TAK-788) is an inhibitor of EGFR and HER2 oncogenic mutants, including exon 20 insertions.

In vitro activity:

To confirm the Ba/F3 preclinical model findings, this study used a second set of preclinical systems with patient-derived lung adenocarcinoma cell lines. The EGFR-A763_Y764insFQEA-bearing BID007 cells and the EGFR-N771_H772insH-bearing BID019 cells were inhibited by mobocertinib in a dose-dependent manner (Fig.2A) similar to the Ba/F3 counterpart results (Fig.1). Cell lines harboring the EGFR-TKI sensitive EGFR-delE746_A750 mutation (PC-9) were the most sensitive while lines harboring the erlotinib/afatinib/poziotinib resistant EGFR-L858R+T790M mutation (H1975) were the least sensitive (Fig.2A). Reference: JTO Clin Res Rep. 2021 Mar; 2(3): 100105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959160/

In vivo activity:

This study evaluated mobocertinib in two mouse tumor models containing an EGFRex20ins ASV mutation. In a tumor model using engineered Ba/F3 cells, once-daily oral dosing of mobocertinib showed dose-dependent inhibition of tumor growth, or tumor regression, at well-tolerated doses (Supplementary Fig. S1A and S1B). In a xenograft model using CTG-2842 cells from a patient with EGFRex20ins ASV-mutant NSCLC who had been treated with erlotinib (without response), mobocertinib dosed orally at 15 mg/kg daily induced substantial tumor regression (92%; Fig. 4A) and was well tolerated (Supplementary Fig. S2). Reference: Cancer Discov. 2021 Feb 25:candisc.1683.2020. https://cancerdiscovery.aacrjournals.org/content/11/7/1672.long

	Solvent	mg/mL	mM
Solubility
	DMSO	17.0	29.02
	DMF	10.0	17.07
	DMF:PBS (pH 7.2) (1:8)	0.1	0.19

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 585.71 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. Vasconcelos PENS, Kobayashi IS, Kobayashi SS, Costa DB. Preclinical characterization of mobocertinib highlights the putative therapeutic window of this novel EGFR inhibitor to EGFR exon 20 insertion mutations. JTO Clin Res Rep. 2021 Mar;2(3):100105. doi: 10.1016/j.jtocrr.2020.100105. Epub 2020 Oct 6. PMID: 33728415; PMCID: PMC7959160. 2. Gonzalvez F, Vincent S, Baker TE, Gould AE, Li S, Wardwell SD, Nadworny S, Ning Y, Zhang S, Huang WS, Hu Y, Li F, Greenfield MT, Zech SG, Das B, Narasimhan NI, Clackson T, Dalgarno D, Shakespeare WC, Fitzgerald M, Chouitar J, Griffin RJ, Liu S, Wong KK, Zhu X, Rivera VM. Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer. Cancer Discov. 2021 Feb 25:candisc.1683.2020. doi: 10.1158/2159-8290.CD-20-1683. Epub ahead of print. PMID: 33632773.

In vitro protocol:

In vivo protocol:

1. Gonzalvez F, Vincent S, Baker TE, Gould AE, Li S, Wardwell SD, Nadworny S, Ning Y, Zhang S, Huang WS, Hu Y, Li F, Greenfield MT, Zech SG, Das B, Narasimhan NI, Clackson T, Dalgarno D, Shakespeare WC, Fitzgerald M, Chouitar J, Griffin RJ, Liu S, Wong KK, Zhu X, Rivera VM. Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer. Cancer Discov. 2021 Jul;11(7):1672-1687. doi: 10.1158/2159-8290.CD-20-1683. Epub 2021 Feb 25. PMID: 33632773. 2. Han H, Li S, Chen T, Fitzgerald M, Liu S, Peng C, Tang KH, Cao S, Chouitar J, Wu J, Peng D, Deng J, Gao Z, Baker TE, Li F, Zhang H, Pan Y, Ding H, Hu H, Pyon V, Thakurdin C, Papadopoulos E, Tang S, Gonzalvez F, Chen H, Rivera VM, Brake R, Vincent S, Wong KK. Targeting HER2 Exon 20 Insertion-Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib. Cancer Res. 2021 Oct 15;81(20):5311-5324. doi: 10.1158/0008-5472.CAN-21-1526. Epub 2021 Aug 11. PMID: 34380634; PMCID: PMC8530969.