BI-3406
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MedKoo CAT#: 207113

CAS#: 2230836-55-0

Description: BI-3406 is Potent & Selective SOS1::KRAS Inhibitor (IC50=5 nM), which Opens a New Approach for Treating KRAS-Driven Tumours. BI 3406 selectively binds to SOS1 and blocks the interaction with KRAS, irrespective of the KRAS mutation. BI 3406 causes RAS GTP and pERK reduction and inhibits cell growth of KRAS mutated cell lines, carrying most of the typical KRAS mutations (i.e. G12D, G12V, G13D and others). BI 3406, when administered orally to tumour bearing mice, causes a dose dependent tumour static effect that can be converted into regressions when combined with MEK1 inhibition.


Chemical Structure

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BI-3406
CAS# 2230836-55-0

Theoretical Analysis

MedKoo Cat#: 207113
Name: BI-3406
CAS#: 2230836-55-0
Chemical Formula: C23H25F3N4O3
Exact Mass: 462.1879
Molecular Weight: 462.4732
Elemental Analysis: C, 59.73; H, 5.45; F, 12.32; N, 12.11; O, 10.38

Price and Availability

Size Price Availability Quantity
50.0mg USD 550.0 2 Weeks
100.0mg USD 950.0 2 Weeks
200.0mg USD 1650.0 2 Weeks
500.0mg USD 3250.0 2 Weeks
1.0g USD 4850.0 2 Weeks
2.0g USD 8250.0 2 Weeks
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Synonym: BI-3406; BI 3406; BI3406;

IUPAC/Chemical Name: N-((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)-7-methoxy-2-methyl-6-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-4-amine

InChi Key: XVFDNRYZXDHTHT-PXAZEXFGSA-N

InChi Code: InChI=1S/C23H25F3N4O3/c1-12(14-6-15(23(24,25)26)8-16(27)7-14)28-22-18-9-21(33-17-4-5-32-11-17)20(31-3)10-19(18)29-13(2)30-22/h6-10,12,17H,4-5,11,27H2,1-3H3,(H,28,29,30)/t12-,17+/m1/s1

SMILES Code: C[C@H](C1=CC(N)=CC(C(F)(F)F)=C1)NC2=C3C(C=C(OC)C(O[C@H]4CCOC4)=C3)=NC(C)=N2

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

Product Data:

Biological target: BI-3406 is an inhibitor of the interaction between KRAS and SOS1 with an IC50 of 6 nM.
In vitro activity: To investigate whether BI-3406 was capable of cellular SOS1 inhibition, cells were treated with increasing concentrations of BI-3406. The compound inhibited RAS-GTP levels with an IC50 of 83–231 nM in SOS1/KRAS-dependent NCI-H358 (KRAS G12C) and A549 (KRAS G12S) cells (Fig. 1g). Furthermore, BI-3406 inhibited the 3D growth of 4 KRAS mutant cancer cells with a IC50 of 16–52 nM, as half-maximum inhibitory concentration (Fig. 2b). Collectively, these data show a clear correlation between signaling pathway and growth inhibition by BI-3406 in KRAS-driven cancer cell lines. Reference: Cancer Discov. 2021 Jan;11(1):142-157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892644/
In vivo activity: Based on its potent cellular activity and favorable pharmacokinetic properties, the efficacy of BI-3406 was evaluated in established, subcutaneous KRAS G12C-mutated MIA PaCa-2 xenografts. Twice daily treatment with either 12 or 50 mg/kg of BI-3406 was well tolerated and resulted in a prolonged dose-dependent tumor growth inhibition (p<0.005 as compared to vehicle control, Fig. 3d, 3e). Similar tumor growth inhibitory effects were observed in KRAS G12V-mutated SW620, the KRAS G13D-mutated LoVo and the KRAS G12S-mutated A549 xenograft models (Fig. 3f, Supplementary Fig. S3i and S3j). Thus, oral administration of BI-3406 monotherapy inhibits the growth of KRAS G12C, G12V, G13D and G12S mutated xenograft models. Reference: Cancer Discov. 2021 Jan;11(1):142-157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892644/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 216.23
Ethanol 100.0 216.23

Preparing Stock Solutions

The following data is based on the product molecular weight 462.4732 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. Hofmann MH, Gmachl M, Ramharter J, Savarese F, Gerlach D, Marszalek JR, Sanderson MP, Kessler D, Trapani F, Arnhof H, Rumpel K, Botesteanu DA, Ettmayer P, Gerstberger T, Kofink C, Wunberg T, Zoephel A, Fu SC, Teh JL, Böttcher J, Pototschnig N, Schachinger F, Schipany K, Lieb S, Vellano CP, O'Connell JC, Mendes RL, Moll J, Petronczki M, Heffernan TP, Pearson M, McConnell DB, Kraut N. BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition. Cancer Discov. 2021 Jan;11(1):142-157. doi: 10.1158/2159-8290.CD-20-0142. Epub 2020 Aug 19. PMID: 32816843; PMCID: PMC7892644.
In vitro protocol: 1. Hofmann MH, Gmachl M, Ramharter J, Savarese F, Gerlach D, Marszalek JR, Sanderson MP, Kessler D, Trapani F, Arnhof H, Rumpel K, Botesteanu DA, Ettmayer P, Gerstberger T, Kofink C, Wunberg T, Zoephel A, Fu SC, Teh JL, Böttcher J, Pototschnig N, Schachinger F, Schipany K, Lieb S, Vellano CP, O'Connell JC, Mendes RL, Moll J, Petronczki M, Heffernan TP, Pearson M, McConnell DB, Kraut N. BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition. Cancer Discov. 2021 Jan;11(1):142-157. doi: 10.1158/2159-8290.CD-20-0142. Epub 2020 Aug 19. PMID: 32816843; PMCID: PMC7892644.
In vivo protocol: 1. Hofmann MH, Gmachl M, Ramharter J, Savarese F, Gerlach D, Marszalek JR, Sanderson MP, Kessler D, Trapani F, Arnhof H, Rumpel K, Botesteanu DA, Ettmayer P, Gerstberger T, Kofink C, Wunberg T, Zoephel A, Fu SC, Teh JL, Böttcher J, Pototschnig N, Schachinger F, Schipany K, Lieb S, Vellano CP, O'Connell JC, Mendes RL, Moll J, Petronczki M, Heffernan TP, Pearson M, McConnell DB, Kraut N. BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition. Cancer Discov. 2021 Jan;11(1):142-157. doi: 10.1158/2159-8290.CD-20-0142. Epub 2020 Aug 19. PMID: 32816843; PMCID: PMC7892644.

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BI-3406

50.0mg / USD 550.0