Bafetinib
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MedKoo CAT#: 200316

CAS#: 859212-16-1

Description: 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

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Bafetinib
CAS# 859212-16-1

Theoretical Analysis

MedKoo Cat#: 200316
Name: Bafetinib
CAS#: 859212-16-1
Chemical Formula: C30H31F3N8O
Exact Mass: 576.26
Molecular Weight: 576.610
Elemental Analysis: C, 62.49; H, 5.42; F, 9.88; N, 19.43; O, 2.77

Price and Availability

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10mg USD 150 Same day
25mg USD 250 Same day
50mg USD 450 Same day
100mg USD 750 Same day
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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.

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 42.0 72.84

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.

Recalculate based on batch purity %
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: 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 vivo 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.

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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.


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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.


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