BI-3406 | CAS#2230836-55-0 | SOS1::KRAS inhibitor

MedKoo Cat#: 207113 | Name: BI-3406

Description:

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

BI-3406 is a potent and selective SOS1::KRAS inhibitor (IC50=5 nM), which opens a new approach for treating KRAS-driven tumors. 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 tumor bearing mice, causes a dose dependent tumor static effect that can be converted into regressions when combined with MEK1 inhibition.

Chemical Structure

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: 462.47

Elemental Analysis: C, 59.73; H, 5.45; F, 12.32; N, 12.11; O, 10.38

Price and Availability

Size	Price	Availability
5mg	USD 95.00	Ready to ship
10mg	USD 170.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship

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Related CAS #

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A23T12K23

QC Data

View QC data: current batch, Lot#A23T12K23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

BI-3406 is an inhibitor of the interaction between KRAS and SOS1 with an IC50 of 6 nM.

In vitro activity:

This study confirmed inhibition of KRAS and its downstream pathways as a potential novel therapy for pancreatic ductal adenocarcinoma (PDAC). BI-3406 alone or in combination with trametinib (MEK1/2 inhibitor) and/or buparlisib (PI3K inhibitor) exhibited cytotoxicity against specific PDAC cell lines. BI-3406 enhanced the efficacy of trametinib and buparlisib in BXPC-3, ASPC-1 and MIA PACA-2, but not in CAPAN-1. Reference: Cancers (Basel). 2022 Sep 14;14(18):4467. https://pubmed.ncbi.nlm.nih.gov/36139627/

In vivo activity:

Oral administration of BI-3406 monotherapy inhibits the growth of KRAS G12C, G12V, G13D and G12S mutated xenograft models. In 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. 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. Reference: Cancer Discov. 2021 Jan;11(1):142-157. https://pubmed.ncbi.nlm.nih.gov/32816843/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	216.23
	Ethanol	100.0	216.23

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 462.47 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. Ma Y, Schulz B, Trakooljul N, Al Ammar M, Sekora A, Sender S, Hadlich F, Zechner D, Weiss FU, Lerch MM, Jaster R, Junghanss C, Murua Escobar H. Inhibition of KRAS, MEK and PI3K Demonstrate Synergistic Anti-Tumor Effects in Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers (Basel). 2022 Sep 14;14(18):4467. doi: 10.3390/cancers14184467. PMID: 36139627; PMCID: PMC9497071. 2. Sheffels E, Kortum RL. Breaking Oncogene Addiction: Getting RTK/RAS-Mutated Cancers off the SOS. J Med Chem. 2021 May 27;64(10):6566-6568. doi: 10.1021/acs.jmedchem.1c00698. Epub 2021 May 7. PMID: 33961431. 3. 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:

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.

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. 2: Thatikonda V, Lyu H, Jurado S, Kostyrko K, Bristow CA, Albrecht C, Alpar D, Arnhof H, Bergner O, Bosch K, Feng N, Gao S, Gerlach D, Gmachl M, Hinkel M, Lieb S, Jeschko A, Machado AA, Madensky T, Marszalek ED, Mahendra M, Melo-Zainzinger G, Molkentine JM, Jaeger PA, Peng DH, Schenk RL, Sorokin A, Strauss S, Trapani F, Kopetz S, Vellano CP, Petronczki M, Kraut N, Heffernan TP, Marszalek JR, Pearson M, Waizenegger IC, Hofmann MH. Co-targeting SOS1 enhances the antitumor effects of KRAS^G12C inhibitors by addressing intrinsic and acquired resistance. Nat Cancer. 2024 Sep;5(9):1352-1370. doi: 10.1038/s43018-024-00800-6. Epub 2024 Aug 5. PMID: 39103541; PMCID: PMC11424490. 3: Koga T, Suda K, Fujino T, Ohara S, Hamada A, Nishino M, Chiba M, Shimoji M, Takemoto T, Arita T, Gmachl M, Hofmann MH, Soh J, Mitsudomi T. KRAS Secondary Mutations That Confer Acquired Resistance to KRAS G12C Inhibitors, Sotorasib and Adagrasib, and Overcoming Strategies: Insights From In Vitro Experiments. J Thorac Oncol. 2021 Aug;16(8):1321-1332. doi: 10.1016/j.jtho.2021.04.015. Epub 2021 May 7. PMID: 33971321. 4: Daley BR, Sealover NE, Sheffels E, Hughes JM, Gerlach D, Hofmann MH, Kostyrko K, Mair B, Linke A, Beckley Z, Frank A, Dalgard C, Kortum RL. SOS1 inhibition enhances the efficacy of and delays resistance to G12C inhibitors in lung adenocarcinoma. bioRxiv [Preprint]. 2023 Dec 15:2023.12.07.570642. doi: 10.1101/2023.12.07.570642. Update in: Cancer Res. 2025 Jan 2;85(1):118-133. doi: 10.1158/0008-5472.CAN-23-3256. PMID: 38106234; PMCID: PMC10723384. 5: Daley BR, Vieira HM, Rao C, Hughes JM, Beckley ZM, Huisman DH, Chatterjee D, Sealover NE, Cox K, Askew JW, Svoboda RA, Fisher KW, Lewis RE, Kortum RL. SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status. Proc Natl Acad Sci U S A. 2023 Nov 21;120(47):e2313137120. doi: 10.1073/pnas.2313137120. Epub 2023 Nov 16. PMID: 37972068; PMCID: PMC10666034. 6: Kessler D, Gerlach D, Kraut N, McConnell DB. Targeting Son of Sevenless 1: The pacemaker of KRAS. Curr Opin Chem Biol. 2021 Jun;62:109-118. doi: 10.1016/j.cbpa.2021.02.014. Epub 2021 Apr 10. PMID: 33848766. 7: Daley BR, Sealover NE, Finniff BA, Hughes JM, Sheffels E, Gerlach D, Hofmann MH, Kostyrko K, LaMorte JP, Linke AJ, Beckley Z, Frank AM, Lewis RE, Wilkerson MD, Dalgard CL, Kortum RL. SOS1 Inhibition Enhances the Efficacy of KRASG12C Inhibitors and Delays Resistance in Lung Adenocarcinoma. Cancer Res. 2025 Jan 2;85(1):118-133. doi: 10.1158/0008-5472.CAN-23-3256. PMID: 39437166; PMCID: PMC11695159. 8: Thatikonda V, Lu H, Jurado S, Kostyrko K, Bristow CA, Bosch K, Feng N, Gao S, Gerlach D, Gmachl M, Lieb S, Jeschko A, Machado AA, Marszalek ED, Mahendra M, Jaeger PA, Sorokin A, Strauss S, Trapani F, Kopetz S, Vellano CP, Petronczki M, Kraut N, Heffernan TP, Marszalek JR, Pearson M, Waizenegger I, Hofmann MH. Combined KRAS^G12C and SOS1 inhibition enhances and extends the anti- tumor response in KRAS^G12C-driven cancers by addressing intrinsic and acquired resistance. bioRxiv [Preprint]. 2023 Jan 23:2023.01.23.525210. doi: 10.1101/2023.01.23.525210. Update in: Nat Cancer. 2024 Sep;5(9):1352-1370. doi: 10.1038/s43018-024-00800-6. PMID: 36747713; PMCID: PMC9900819. 9: Jackson M, Ahmari N, Wu J, Rizvi TA, Fugate E, Kim MO, Dombi E, Arnhof H, Boehmelt G, Düchs MJ, Long CJ, Maier U, Trapani F, Hofmann MH, Ratner N. Combining SOS1 and MEK Inhibitors in a Murine Model of Plexiform Neurofibroma Results in Tumor Shrinkage. J Pharmacol Exp Ther. 2023 May;385(2):106-116. doi: 10.1124/jpet.122.001431. Epub 2023 Feb 27. PMID: 36849412; PMCID: PMC10108440. 10: Luo Z, Lin C, Yu C, Yuan C, Wu W, Xu X, Sun R, Jia Y, Wang Y, Shen J, Wang D, Wang S, Jiang H, Jiang B, Yang X, Xie C. Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia. Cancer Res. 2025 Jan 2;85(1):101-117. doi: 10.1158/0008-5472.CAN-24-1093. PMID: 39437162; PMCID: PMC11694061.