Synonym
BI-2865; BI 2865; BI2865;
IUPAC/Chemical Name
(S)-2-amino-4-methyl-4-(3-(4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)pyrimidin-2-yl)-1,2,4-oxadiazol-5-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile
InChi Key
MIUFORKWYHBPRW-HMFCALDFSA-N
InChi Code
InChI=1S/C23H27N7O2S/c1-13(15-6-5-11-30(15)3)31-17-8-10-26-20(27-17)21-28-22(32-29-21)23(2)9-4-7-16-18(23)14(12-24)19(25)33-16/h8,10,13,15H,4-7,9,11,25H2,1-3H3/t13-,15-,23-/m0/s1
SMILES Code
N#CC1=C(N)SC2=C1[C@@](C)(C3=NC(C4=NC(O[C@@H](C)[C@@H]5CCCN5C)=CC=N4)=NO3)CCC2
Appearance
To be determined
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
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
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
KRAS is one of the most commonly mutated proteins in cancer, and efforts to directly inhibit its function have been continuing for decades. The most successful of these has been the development of covalent allele-specific inhibitors that trap KRAS G12C in its inactive conformation and suppress tumour growth in patients.
Biological target:
Pan-KRAS inhibitor, mean IC50: roughly 140 nM.
In vitro activity:
Inhibition of the latter state suppressed downstream signaling and cancer cell proliferation in vitro and in mouse xenografts. Moreover, a non-covalent pan-KRAS inhibitor, BI-2865, reduced tumor proliferation in cell lines and mouse models. Finally, the next generation of KRAS mutant-specific and pan-RAS tri-complex inhibitors have revolutionized RAS drug discovery.
Reference:
Lokhandwala J, Smalley TB, Tran TH. Structural perspectives on recent breakthrough efforts toward direct drugging of RAS and acquired resistance. Front Oncol. 2024 May 22;14:1394702. doi: 10.3389/fonc.2024.1394702. PMID: 38841166; PMCID: PMC11150659.
In vivo activity:
The cytotoxicity of BI-2865 and its MDR removal effect in vitro were tested by MTT assays, and the corresponding reversal function in vivo was assessed through the P-gp mediated KBv200 xenografts in mice. BI-2865 induced alterations of drug discharge and reservation in cells were estimated by experiments of Flow cytometry with fluorescent doxorubicin, and the chemo-drug accumulation in xenografts' tumor were analyzed through LC-MS.
Reference:
Yang Q, To KKW, Hu G, Fu K, Yang C, Zhu S, Pan C, Wang F, Luo K, Fu L. BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo. Cell Commun Signal. 2024 Jun 13;22(1):325. doi: 10.1186/s12964-024-01698-4. PMID: 38872211; PMCID: PMC11170860.
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
250.0 |
536.98 |
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
465.58
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 |
In vitro protocol:
1: Yang Q, To KKW, Hu G, Fu K, Yang C, Zhu S, Pan C, Wang F, Luo K, Fu L. BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo. Cell Commun Signal. 2024 Jun 13;22(1):325. doi: 10.1186/s12964-024-01698-4. PMID: 38872211; PMCID: PMC11170860.
2: Lokhandwala J, Smalley TB, Tran TH. Structural perspectives on recent breakthrough efforts toward direct drugging of RAS and acquired resistance. Front Oncol. 2024 May 22;14:1394702. doi: 10.3389/fonc.2024.1394702. PMID: 38841166; PMCID: PMC11150659.
In vivo protocol:
1: Yang Q, To KKW, Hu G, Fu K, Yang C, Zhu S, Pan C, Wang F, Luo K, Fu L. BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo. Cell Commun Signal. 2024 Jun 13;22(1):325. doi: 10.1186/s12964-024-01698-4. PMID: 38872211; PMCID: PMC11170860.
2: Choi J, Shin JY, Kim TK, Kim K, Kim J, Jeon E, Park J, Han YD, Kim KA, Sim T, Kim HK, Kim HS. Site-specific mutagenesis screening in KRASG12D mutant library to uncover resistance mechanisms to KRASG12D inhibitors. Cancer Lett. 2024 Jun 1;591:216904. doi: 10.1016/j.canlet.2024.216904. Epub 2024 Apr 18. PMID: 38642608.
Kim D, Herdeis L, Rudolph D, Zhao Y, Böttcher J, Vides A, Ayala-Santos CI, Pourfarjam Y, Cuevas-Navarro A, Xue JY, Mantoulidis A, Bröker J, Wunberg T, Schaaf O, Popow J, Wolkerstorfer B, Kropatsch KG, Qu R, de Stanchina E, Sang B, Li C, McConnell DB, Kraut N, Lito P. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature. 2023 Jul;619(7968):160-166. doi: 10.1038/s41586-023-06123-3. Epub 2023 May 31. PMID: 37258666; PMCID: PMC10322706.
