Bafetinib | INNO-406 | NS-187 | CAS#887650-05-7 | Bcr/Abl inhibitor

MedKoo Cat#: 200316 | Name: Bafetinib

Description:

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

Bafetinib, also known as INNO-406 and NS187, is an orally bioavailable 2-phenylaminopyrimidine derivative with potential antineoplastic activity. Bafetinib specifically binds to and inhibits the Bcr/Abl fusion protein tyrosine kinase, an abnormal enzyme produced by Philadelphia chromosomal translocation associated with chronic myeloid leukemia (CML). This agent also inhibits the Src-family member Lyn tyrosine kinase, upregulated in imatinib-resistant CML cells and in a variety of solid cancer cell types.

Chemical Structure

Bafetinib

CAS#859212-16-1

Theoretical Analysis

MedKoo Cat#: 200316

Name: Bafetinib

CAS#: 859212-16-1

Chemical Formula: C30H31F3N8O

Exact Mass: 576.2573

Molecular Weight: 576.61

Elemental Analysis: C, 62.49; H, 5.42; F, 9.88; N, 19.43; O, 2.77

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 425.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship

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Related CAS #

859212-16-1 887650-05-7

Synonym

INNO406; INNO-406; INNO 406; NS187; NS-187; NS 187; Bafetinib.

IUPAC/Chemical Name

(S)-N-(3-([4,5'-bipyrimidin]-2-ylamino)-4-methylphenyl)-4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)benzamide

InChi Key

ZGBAJMQHJDFTQJ-DEOSSOPVSA-N

InChi Code

InChI=1S/C30H31F3N8O/c1-19-4-7-23(13-27(19)39-29-36-10-8-26(38-29)22-14-34-18-35-15-22)37-28(42)20-5-6-21(25(12-20)30(31,32)33)16-41-11-9-24(17-41)40(2)3/h4-8,10,12-15,18,24H,9,11,16-17H2,1-3H3,(H,37,42)(H,36,38,39)/t24-/m0/s1

SMILES Code

O=C(NC1=CC=C(C)C(NC2=NC=CC(C3=CN=CN=C3)=N2)=C1)C4=CC=C(CN5C[C@@H](N(C)C)CC5)C(C(F)(F)F)=C4

Appearance

white 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

The inhibitory effect of bafetinib on these specific tyrosine kinases may decrease cellular proliferation and induce apoptosis in tumor cells that overexpress these kinases. CML patients may be refractory to imatinib, which sometimes results from point mutations occurring in the kinase domain of the Bcr/Abl fusion product. Due to its dual inhibitory activity, the use of bafetinib has been shown to overcome this particular drug resistance.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A20T07K23

QC Data

View QC data: current batch, Lot#A20T07K23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Bafetinib is a Lyn and Bcr-Abl tyrosine kinase inhibitor.

In vitro activity:

Bafetinib (1–10 μM) concentration dependently inhibited PAR2-TRPV4 coupling. In TRPV4 HEKs, 10 μM bafetinib significantly inhibited the coupling response to SLIGRL (F340/F380 ratio 0.39 ± 0.04) and trypsin (0.52 ± 0.06) compared with vehicle control (0.66 ± 0.06 and 1.01 ± 0.11 respectively) (P < 0.05) (Figure 3). Conversely, bafetinib did not affect peak PAR2 or GSK1016790A responses (P > 0.05). Thus, bafetinib inhibits the signalling pathway leading to TRPV4 channel opening, downstream of PAR2 activation, most likely by blocking the activation of a tyrosine kinase. Reference: Br J Pharmacol. 2014 Aug;171(16):3881-94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128050/

In vivo activity:

To investigate whether tyrosine kinase activity mediates this hypersensitivity, C57BL/6 mice were treated with vehicle or bafetinib (10 mg·kg−1) by oral gavage 30 min prior to intraplantar injection of the PAR2 agonist SLIGRL into the left hind paw. von Frey mechanical pain threshold was subsequently measured at 0.5, 1, 2, 3 and 4 h after paw injection (for both the treated and non-treated paws). PAR2 activation caused marked mechanical hyperalgesia in the left paw of the vehicle-treated animals. Compared with vehicle controls, pretreatment of mice with bafetinib inhibited PAR2-induced mechanical hyperalgesia at all time points (P < 0.05) (Figure (Figure 7A). Unexpectedly, bafetinib also inhibited the GSK1016790A-mediated hyperalgesic response compared with controls (P < 0.05; Figure 6C). Reference: Br J Pharmacol. 2014 Aug;171(16):3881-94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128050/

	Solvent	mg/mL	mM
Solubility
	DMSO	42.0	72.84

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 576.61 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. Grace MS, Lieu T, Darby B, Abogadie FC, Veldhuis N, Bunnett NW, McIntyre P. The tyrosine kinase inhibitor bafetinib inhibits PAR2-induced activation of TRPV4 channels in vitro and pain in vivo. Br J Pharmacol. 2014 Aug;171(16):3881-94. doi: 10.1111/bph.12750. PMID: 24779362; PMCID: PMC4128050.

In vitro protocol:

In vivo protocol:

1: Chen X, Du Q, Guo H, He Q, Yang B, Ding L. Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer. Front Pharmacol. 2022 Jun 2;13:897747. doi: 10.3389/fphar.2022.897747. PMID: 35721177; PMCID: PMC9201485. 2: Santos FP, Kantarjian H, Cortes J, Quintas-Cardama A. Bafetinib, a dual Bcr- Abl/Lyn tyrosine kinase inhibitor for the potential treatment of leukemia. Curr Opin Investig Drugs. 2010 Dec;11(12):1450-65. PMID: 21154127. 3: Milara J, Martinez-Losa M, Sanz C, Almudéver P, Peiró T, Serrano A, Morcillo EJ, Zaragozá C, Cortijo J. Bafetinib inhibits functional responses of human eosinophils in vitro. Eur J Pharmacol. 2013 Sep 5;715(1-3):172-80. doi: 10.1016/j.ejphar.2013.05.025. Epub 2013 Jun 6. PMID: 23747655. 4: Zhang YK, Zhang GN, Wang YJ, Patel BA, Talele TT, Yang DH, Chen ZS. Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters. Sci Rep. 2016 May 9;6:25694. doi: 10.1038/srep25694. PMID: 27157787; PMCID: PMC4860574. 5: Rossari F, Minutolo F, Orciuolo E. Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy. J Hematol Oncol. 2018 Jun 20;11(1):84. doi: 10.1186/s13045-018-0624-2. PMID: 29925402; PMCID: PMC6011351. 6: Burkard TR, Rix U, Breitwieser FP, Superti-Furga G, Colinge J. A computational approach to analyze the mechanism of action of the kinase inhibitor bafetinib. PLoS Comput Biol. 2010 Nov 18;6(11):e1001001. doi: 10.1371/journal.pcbi.1001001. PMID: 21124949; PMCID: PMC2987840. 7: Portnow J, Badie B, Markel S, Liu A, D'Apuzzo M, Frankel P, Jandial R, Synold TW. A neuropharmacokinetic assessment of bafetinib, a second generation dual BCR-Abl/Lyn tyrosine kinase inhibitor, in patients with recurrent high-grade gliomas. Eur J Cancer. 2013 May;49(7):1634-40. doi: 10.1016/j.ejca.2013.01.001. Epub 2013 Feb 4. PMID: 23380277; PMCID: PMC4172445. 8: Yang X, Miao Y, Wang J, Mi D. A pan-cancer analysis of the HER family gene and their association with prognosis, tumor microenvironment, and therapeutic targets. Life Sci. 2021 May 15;273:119307. doi: 10.1016/j.lfs.2021.119307. Epub 2021 Mar 8. PMID: 33691171. 9: Grace MS, Lieu T, Darby B, Abogadie FC, Veldhuis N, Bunnett NW, McIntyre P. The tyrosine kinase inhibitor bafetinib inhibits PAR2-induced activation of TRPV4 channels in vitro and pain in vivo. Br J Pharmacol. 2014 Aug;171(16):3881-94. doi: 10.1111/bph.12750. PMID: 24779362; PMCID: PMC4128050. 10: Peter B, Hadzijusufovic E, Blatt K, Gleixner KV, Pickl WF, Thaiwong T, Yuzbasiyan-Gurkan V, Willmann M, Valent P. KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406). Exp Hematol. 2010 Sep;38(9):782-91. doi: 10.1016/j.exphem.2010.05.004. Epub 2010 May 26. PMID: 20685234. 11: Kimura S, Ando T, Kojima K. Ever-advancing chronic myeloid leukemia treatment. Int J Clin Oncol. 2014 Feb;19(1):3-9. doi: 10.1007/s10147-013-0641-7. Epub 2013 Nov 22. PMID: 24258348. 12: Fowler AJ, Hebron M, Missner AA, Wang R, Gao X, Kurd-Misto BT, Liu X, Moussa CE. Multikinase Abl/DDR/Src Inhibition Produces Optimal Effects for Tyrosine Kinase Inhibition in Neurodegeneration. Drugs R D. 2019 Jun;19(2):149-166. doi: 10.1007/s40268-019-0266-z. PMID: 30919310; PMCID: PMC6544596. 13: Green MR, Newton MD, Fancher KM. Off-Target Effects of BCR-ABL and JAK2 Inhibitors. Am J Clin Oncol. 2016 Feb;39(1):76-84. doi: 10.1097/COC.0000000000000023. PMID: 24351780. 14: Leonetti F, Stefanachi A, Nicolotti O, Catto M, Pisani L, Cellamare S, Carotti A. BCR-ABL inhibitors in chronic myeloid leukemia: process chemistry and biochemical profile. Curr Med Chem. 2011;18(19):2943-59. doi: 10.2174/092986711796150414. PMID: 21651486. 15: Kimura S. [Development of ABL tyrosine kinase inhibitors]. Rinsho Ketsueki. 2010 Aug;51(8):597-604. Japanese. PMID: 20805664. 16: Jakubowska J, Czyz M. Alternatywne dla STI571 inhibitory kinazy Bcr-Abl [Novel inhibitors of Bcr-Abl]. Postepy Hig Med Dosw (Online). 2006;60:697-706. Polish. PMID: 17245319. 17: Robak T, Robak E. Tyrosine kinase inhibitors as potential drugs for B-cell lymphoid malignancies and autoimmune disorders. Expert Opin Investig Drugs. 2012 Jul;21(7):921-47. doi: 10.1517/13543784.2012.685650. Epub 2012 May 22. PMID: 22612424. 18: Serra A, Fratello M, Federico A, Ojha R, Provenzani R, Tasnadi E, Cattelani L, Del Giudice G, Kinaret PAS, Saarimäki LA, Pavel A, Kuivanen S, Cerullo V, Vapalahti O, Horvath P, Lieto AD, Yli-Kauhaluoma J, Balistreri G, Greco D. Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation. Brief Bioinform. 2022 Jan 17;23(1):bbab507. doi: 10.1093/bib/bbab507. PMID: 34962256; PMCID: PMC8769897. 19: Müller BA. Imatinib and its successors--how modern chemistry has changed drug development. Curr Pharm Des. 2009;15(2):120-33. doi: 10.2174/138161209787002933. PMID: 19149608. 20: Kong E, Li Y, Ma P, Zhang Y, Ding R, Hua T, Yang M, Yuan H. Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn. J Cell Mol Med. 2023 Jun;27(12):1664-1681. doi: 10.1111/jcmm.17759. Epub 2023 May 2. PMID: 37132040; PMCID: PMC10273059.