Ras Inhibitor

AMG410 is a non-covalent and selective pan-KRAS inhibitor with IC₅₀ values of 1-4 nM for KRAS G12D, KRAS G12V, and KRAS G13D. AMG410 shows greater than 100-fold selectivity against both HRAS and NRAS. AMG410 is a dual GTP(on)- and GDP(off)-state inhibitor (K_d(GDP-state) of 1 nM; K_d(GTP-state) of 22 nM). AMG410 blocks KRAS signaling in a cycling state-independent manner and also blocks proliferation in wildtype KRAS-amplified tumor cells. AMG410 can be used for the study of colorectal, pancreatic, and lung cancers.

Setidegrasib (ASP-3082) is a PROTAC KRAS degrader (DC₅₀: 37 nM). Setidegrasib induces the degradation of G12D-mutation KRAS protein. Setidegrasib suppresses p-ERK, p-AKT, p-S6 levels in AsPC-1 cells. Setidegrasib exhibits anti-tumor activity in various cancer xenograft models in mice. Setidegrasib can be used in studies involving KRAS(G12D)-mutated solid tumors, such as non-small cell lung cancer.

Grassofermata is a dual Arf1/Arf6 activation inhibitor. ADP ribosylation factors (Arfs) are members of the Arf family of GTP-binding proteins of the Ras superfamily.

RMC-5127 is a small molecule inhibitor that binds to GTP-targeted KRAS^G12V, with oral bioavailability and blood-brain barrier permeability. RMC-5127 inhibits the activities of the RAS and MAPK pathways, suppresses the proliferation of KRAS^G12V-mutant cancer cells and induces their apoptosis. RMC-5127 can be used for the research of KRAS^G12V-mutant non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer and intracranial KRAS^G12V tumors.

HRS-4642 is a high affinity, selective, long-acting, and non-covalent KRAS^G12D inhibitor with a K_d value of 0.083 nM. HRS-4642 inhibits the binding of KRAS^G12D to SOS1 or RAF1, thereby blocking the downstream MEK-ERK signaling pathway. HRS-4642 promotes Apoptosis. HRS-4642 alone or combined with Carfilzomib (HY-10455) effectively shapes the tumor microenvironment. HRS-4642 has an anti-cancer effect on pancreatic and colorectal cancers carrying the KRAS^G12D mutation.

DCC-3116 is an orally active ULK1/2 inhibitor. DCC-3116 can inhibit autophagy in lung cancer cells by inhibiting KRAS^G12C signaling, thereby inhibiting the proliferation of lung cancer cells and exerting anti-cancer effects.

BI-2852 is a KRAS inhibitor for the switch I/II pocket (SI/II-pocket) by structure-based agent design with nanomolar affinity. BI-2852 is mechanistically distinct from covalent KRASG12C inhibitor (binds to switch II pocket) and binds ten-fold more strongly to active KRASG12D versus KRASwt (740 nM vs 7.5 μM). BI-2852 blocks GEF, GAP, and effector interactions with KRAS, leading to inhibition of downstream signaling and an antiproliferative effect in KRAS mutant cells.

EHop-016 is a potent and selective Rac GTPase Rac1 and Rac3 inhibitor. EHop-016 inhibits Rac1 activity with an IC₅₀ of 1.1 μM in MDA-MB-435 cells. EHop-016 inhibits Vav2 interaction with Rac, Rac-activated PAK1, lamellipodia formation, and cell migration.

Nexinhib20 is an inhibitor that targets the interactions of Rab27a-JFC1 (IC₅₀: 2.6 μM) and Rac-1-GTP. Nexinhib20 can inhibit neutrophil exocytosis, adhesion, and β2 integrin activation, and has anti-inflammatory activity. Nexinhib20 can be used in the research of diseases such as systemic inflammation and myocardial ischemia-reperfusion injury.

Rhosin is a potent, specific RhoA subfamily Rho GTPases inhibitor, which specifically binds to RhoA to inhibit RhoA-GEF interaction with a K_d of ~ 0.4 uM, and does not interact with Cdc42 or Rac1, nor the GEF, LARG. Rhosin induces cell apoptosis. Rhosin promotes stress resiliency through enhancing D1-MSN plasticity and reducing hyperexcitability.

CCG-1423 is an inhibitor of Rho/MRTF/SRF pathway. CCG-1423 shows activities in several cancer cells. CCG-1423 is a promising lead compound for the development of novel pharmacologic tools, and it can be used for the research of cancer and diabetes.

Ibetazol is a Importin β1 (KPNB1) inhibitor and nucleocytoplasmic transport disruptor. Ibetazol binds covalently to Cys585 of Importin β1, blocks both Importin β1-mediated direct transport and Importin α-dependent nuclear import processes, without affecting transport mediated by other nucleocytoplasmic transport proteins. Ibetazol induces cytoplasmic accumulation of Importin α1, and inhibits nuclear import of substrates carrying nuclear localization signals (NLS), including the NLS-cMyc reporter gene, RelA/p65 and SREBP1. Ibetazol triggers spindle malformation and chromosome misalignment by disrupting the mitotic function of Importin β1. Ibetazol inhibits the proliferation of cells expressing wild-type Importin β1. Ibetazol has a high activity-cytotoxicity window, lacks intrinsic fluorescence, and acts rapidly on nucleocytoplasmic transport processes. Ibetazol serves as a tool compound for investigating nuclear import processes specifically mediated by Importin β1.

MBQ-167 is a dual Rac/Cdc42 inhibitor, with IC₅₀s of 103 nM for Rac 1/2/3 and 78 nM for Cdc42 in MDA-MB-231 cells, respectively.

Salirasib is a Ras inhibitor that inhibits specifically both oncogenically activated Ras and growth factor receptor-mediated Ras activation, resulting in the inhibition of Ras-dependent tumor growth.

BBO-8520 is a direct small molecule covalent inhibitor targeting KRAS ^G12C with high oral availability. BBO-8520 has the characteristics of KRAS ^G12C (OFF) inhibitor and the function of blocking KRAS^G12C (ON) signal. BBO-8520 inhibits cell proliferation by inhibiting KRAS ^G12C (ON) by binding GTP protein. BBO-8520 can block RAS-RAF1 interaction and return KRAS ^G12C to the inactive (OFF) state. BBO-8520 can be used for the research of cancer.

BBO-10203 is a potent inhibitor of PI3Kα and KRAS^G12C, selectively and covalently binding to Cys242 in the RAS-Binding Domain of PI3Kα, and inhibiting both the GTP-bound and GDP-bound states of KRAS^G12C with an IC₅₀ of 0.031 nM and an EC₅₀ of 0.02 nM. BBO-10203 disrupts the interaction between RAS isoforms and PI3Kα, leading to the inhibition of RAS-mediated PI3Kα activation, and reduces pERK expression, cell growth, and induces G₁ arrest and apoptosis. BBO-10203 can be used for the research of breast cancer, colorectal cancer, and non-small cell lung cancer.

LUNA18 is an orally-available cyclic peptide KRAS and ERK inhibitor. LUNA18 phosphorylates ERK and AKT and decreases cell proliferation in RAS-mutated cancer cells. LUNA18 exhibits RAS signal inhibition and potent anti-cancer activities through inhibiting interaction between RAS and guanine nucleotide exchange factors (GEFs) in a mouse xenograft model. LUNA18 shows significant cellular efficacy against cell lines with KRAS genetic alterations, such as colon cancer, stomach cancer, non-small cell lung cancer and pancreaticcancer.

Manumycin A is a polyketide antibiotic and an inhibitor of thioredoxin reductase 1 (TrxR-1). Manumycin A can inhibit the growth of breast cancer cells and exert its anti-tumor activity through LC3. Manumycin A can downregulate the release of pro-inflammatory cytokines in human monocytes stimulated by TNF α, and has potential anti-inflammatory activity. Manumycin A can inhibit the Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration resistant prostate cancer cells to suppress exosome biogenesis and secretion.

FTI-277 hydrochloride is an inhibitor of farnesyl transferase (FTase); a highly potent Ras CAAX peptidomimetic which antagonizes both H- and K-Ras oncogenic signaling. FTI-277 hydrochloride can inhibit hepatitis delta virus (HDV) infection.

BI-2493 is a structural analogue of BI-2865 and a highly selective and orally active pan-KRAS inhibitor. BI-2493 can attenuate tumor growth. BI-2493 can be used for cancer iseases research.