KRAS G12C inhibitor 31 is a KRAS G12C inhibitor extracted from patent WO2021252339A1, compound 1. KRAS G12C inhibitor 31 can be used for the research of cancer[1].
KRAS inhibitor-18 (compound 3-10) is a potent KRAS G12C inhibitor with an IC50 of 4.74 µM. KRAS inhibitor-18 shows p-ERK inhibition activities with IC50s of 66.4, 11.1 µM in MIA PaCA-2, A549 cells, respectively. KRAS inhibitor-18 has the potential for the research of pancreatic, colorectal, and lung cancers[1].
6H05 is a selective, and allosteric inhibitor of oncogenic mutant K-Ras(G12C). IC50 value:Target: K-Ras G12C6H05 gives the greatest degree of modification, which allosterically modifies the oncogenic G12C mutant of highly homologous protein H-Ras without affecting wild-type K-Ras [1]. 6H05 can be used as an intermediate for the synthesis of other oncogenic K-Ras(G12C) inhibitors [2].
Nexinhib20 is a specific Rab27a-JFC1 interaction inhibitor with a calculated IC50 of 2.6 μM. Nexinhib20 significantly inhibits superoxide anion production. Nexinhib20 efficiently decreases exocytosis of azurophilic granules in neutrophils stimulated with fMLP, GM-CSF or both. Nexinhib20 has a significant anti-inflammatory activity[1].
RM-018 is a potent, functionally distinct tricomplex KRASG12C active-state inhibitor. RM-018 retaines the ability to bind and inhibit KRASG12C/Y96D and could overcome resistance. RM-018 binds specifically to the GTP-bound, active [“RAS(ON)”] state of KRASG12C[1].
ARS-1630 is a novel inhibitor of mutant K-ras G12C extracted from patent WO 2015054572 A1.
ZCL278 is a selective Cdc42 modulator that directly binds to Cdc42 and inhibits its functions with Kd of 11.4 μM for Cdc42-ZCL278 affinity in surface plasmon resonance (SPR) experiment.
KRAS G12D inhibitor 17 (example 8) is a quinazoline-linked (4R)-4-hydroxy-L-prolinamide compound, inducing degradation of G12D-mutation KRAS protein[1].
1A-116 is a specific Rac1 inhibitor.
KRAS G12C inhibitor 17 is a potent KRAS G12C inhibitor extracted from patent WO2019110751A1, compound 82, has an IC50 of 5 nM[1].
PROTAC KRAS G12C degrader-3 (Comp 283) is a potent KRAS G12C degrader for cancer research[1].
KRAS inhibitor-17 (compound 3-9) is a potent KRAS G12C inhibitor with an IC50 of 3.37 µM. KRAS inhibitor-17 shows p-ERK inhibition activities with IC50s of 9.25, >33.3 µM in MIA PaCA-2, A549 cells, respectively. KRAS inhibitor-17 has the potential for the research of pancreatic, colorectal, and lung cancers[1].
KRAS G12C inhibitor 42 is a potent inhibitor of KRAS G12C. The Ras family of proteins is an important intracellular signaling molecule that plays an important role in growth and development. KRAS G12C inhibitor 42 has the potential for the research of KRAS G12C-mediated cancer (extracted from patent WO2020146613A1, compound 10)[1].
ARS-1620 is an atropisomeric selective KRASG12C inhibitor with desirable pharmacokinetics.
KRAS G12C inhibitor 35 is a potent inhibitor of KRAS G12C. The Ras family of proteins is an important intracellular signaling molecule that plays an important role in growth and development. KRAS G12C inhibitor 35 has the potential for the research of KRAS G12C-mediated cancer (extracted from patent CN112920183A, compound 3)[1].
KRAS inhibitor-14 (compound 3-22) is a potent KRAS G12C inhibitor with an IC50 of 0.249 µM. KRAS inhibitor-14 shows p-ERK inhibition activities with IC50s of 1.12, >33.3 µM in MIA PaCA-2, A549 cells, respectively. KRAS inhibitor-14 has the potential for the research of pancreatic, colorectal, and lung cancers[1].
KRAS G12C inhibitor 33 is a KRAS G12C inhibitor extracted from patent WO2021244603A1, compound 1. KRAS G12C inhibitor 33 can be used for the research of cancer[1].
KRAS G12C inhibitor 56 (compound IC-6) is a potent SOS1 inhibitor with an IC50 of 1.6 nM. KRAS G12C inhibitor 56 can be used in cancer research[1].
EHop-016 is a novel potent and selective inhibitor of Rac GTPase; inhibits Rac1 activity in MDA-MB-435 cells with an IC50 of 1.1 uM.IC50 value: 1.1 uM (MDA-MB-435 cell) [1]Target: Rac1 inhibitorin vitro: The IC(50) of 1.1 μM for Rac inhibition by EHop-016 is ～100-fold lower than for NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations of ≤5 μM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells that demonstrate high active levels of the Rac GEF Vav2, EHop-016 inhibits the association of Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac downstream effects of PAK1 (p21-activated kinase 1) activity and directed migration of metastatic cancer cells. Moreover, at effective concentrations (<5 μM), EHop-016 does not affect the viability of transformed mammary epithelial cells (MCF-10A) and reduces viability of MDA-MB-435 cells by only 20% [1]. At higher concentrations (10μM), EHop-016 inhibits the related Rho GTPase Cdc42, but not Rho, and also reduces cell viability. Moreover, EHop-016 inhibits the activation of the Rac downstream effector p21-activated kinase, extension of motile actin-based structures, and cell migration [2].in vivo: As quantified by UPLC MS/MS, EHop-016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016. The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by immunohistochemistry of excised tumors and by In Vitro tube formation assays of endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells [3].
KRAS G12C inhibitor 45 (compound 78) is a potent KRAS G12C inhibitor[1].
K-Ras (G12C) inhibitor 9 is an allosteric inhibitor of the K-Ras (G12C)[1].
KRAS G12C inhibitor 23 is a KRAS G12C inhibitor. KRAS G12C inhibitor 23 inhibits H358 cells with an IC50 of 491 nM (WO2021218939A1, compound 1)[1].
Y16 is an inhibitor of G-protein–coupled Rho GEFs; works synergistically with Rhosin/G04 in inhibiting LARG-RhoA interaction, RhoA activation, and RhoA-mediated signaling functions.IC50 value: Target: RhoA inhibitorY16 binds to this catalytic fragment of LARG with a Kd of ～76 ± 8 nM. Y16 was able to inhibit the GDP dissociation from RhoA catalyzed by LARG dose dependently without affecting the GEF reactions of Rac1 and Cdc42 catalyzed by TrioN and Intersectin, respectively. The N983A mutant lost the binding ability to Y16 with a Kd > 500 μM, whereas the K979A and E982A mutants showed a reduced affinity with Kd values of 0.47 and 2.1 μM, respectively. At 2.5 μM each, Rhosin and Y16 inhibited ～50% RhoA-GTP content, and at 5 μM each ～80% RhoA-GTP stimulated by serum, which were much more potent than the effect of Rhosin/G04 or Y16 acting alone (～80% inhibition at 30 μM). Even under a higher concentration of Y16 and Rhosin/G04 combination (50 μM each) when endogenous RhoA-GTP content was effectively suppressed, no effect on Rac1-GTP or Cdc42-GTP content in cells was observed. Although Rhosin/G04 or Y16 administration alone caused ～50% inhibition of RhoA activity at 10 μM, combined Rhosin/G04 and Y16 reached 70% inhibition of RhoA-GTP or the downstream p-MLC when each was at 2.5 μM.
TUS-007 is a CANDDY molecular, modified from a proteasome inhibitor. However, TUS-007 hardly inhibits proteasome activity. TUS-007 is also an orally active and potent KRAS G12D/V degrader. TUS-007 can be applied in KRAS G12D/V chemical knockdown in cell-free. TUS-007 also exhibits tumor suppression[1]. Note: CANDDY refers to Chemical knockdown with Affinity aNd Degradation DYnamics.
AMG-510 racemate is the racemate of AMG-510. AMG-510 is a potent KRAS G12C covalent inhibitor.
PROTAC KRAS G12C degrader-2 (compound 432) is a modulator of K-Ras protein hydrolysis. PROTAC KRAS G12C degrader-2 is a bifunctional compound, which contain on one end a cereblon inhibitor of apoptosis proteins (IAP) and on the other end a moiety which binds KRAS[1].
Digeranyl bisphophonate is a potent geranylgeranylpyrophosphate (GGPP) synthase inhibitor, which inhibits geranylgeranylation of Rac1.
RBC8 is a novel small molecule inhibitor of Ral GTPase; has IC50 of 3.5 μM in H2122 cell and 3.4 μM in H358 cell.IC50 value:Target: Ral GTPase inhibitorRBC8 or BQU57 treatment showed no further inhibition of colony formation after Ral knockdown. RBC8 and BQU57 showed favorable properties that define good drug candidates. To test the effect of Ral inhibitors on xenograft tumor growth, nude mice were inoculated subcutaneously with H2122 human lung cancer cells and treated intraperitoneally with 50 mg/kg/d of RBC8 for 21 days (except weekends). RBC8 inhibited tumor growth to a similar extent as dual knockdown of RalA and RalB.
SAH-SOS1A is a KRas/son of sevenless 1 (SOS1) interaction inhibitor. SAH-SOS1A binds within nucleotide binding pocket of KRas (Kd values ranges from 106 - 176 nM for wild type KRas and KRas mutants). SAH-SOS1A inhibits nucleotide binding to KRas in a concentration dependent manner.
Oncrasin-1 is a potent and effective anticancer inhibitor that kills various human lung cancer cells with K-Ras mutations at low or submicromolar concentrations; also led to abnormal aggregationof PKCι in nucleus of sensitive cells but not in resistant cells.IC50 value: 1.0 μM(A549, K-ras 12H and p53 Wt) [1]Target: human lung cancer cells with K-Ras mutation; K-Ras/PKCiota pathway inhibitorin vitro: effectively kills various human lung cancer cells with K-Ras mutations at low or submicromolar concentrations. The cytotoxic effects correlated with apoptosis inductionas was evidenced by increase of apoptotic cells and activation of caspase-3 and caspase-8 upon the treatment of oncrasin-1 in sensitive cells.Treatment with oncrasin-1 also led to abnormal aggregationof PKCι in nucleus of sensitive cells but not in resistant cells. Furthermore, oncrasin-1 induced apoptosis was blocked by siRNA of K-Ras or PKCι suggesting that oncrasin-1 is targeted to a novel K-Ras/PKCι pathway [1]. oncrasin-1 treatment led to coaggregation of PKCiota and splicing factors into megaspliceosomes but had no obvious effects on the DNA repair molecule Rad51. Moreover, oncrasin-1 treatment suppressed the phosphorylation of the largest subunit of RNA polymerase II and the expression of intronless reporter genes in sensitive cells but not in resistant cells [2]. in vivo: The in vivo administration of oncrasin-1 suppressed the growth of K-ras mutant human lung tumor xenografts by >70% and prolonged the survival of nude mice bearing these tumors, without causing detectable toxicity [1].