C-Raf Inhibitor

Sorafenib (Bay 43-9006) is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib inhibits tumor growth and metastasis in mouse and rat models. Sorafenib can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

Dabrafenib (GSK2118436A) is an ATP-competitive inhibitor of Raf with IC₅₀s of 5 nM and 0.6 nM for C-Raf and B-Raf^V600E, respectively.

Vemurafenib (PLX4032) is a first-in-class, selective, potent inhibitor of B-RAF kinase, with IC₅₀s of 31 and 48 nM for RAF^V600E and c-RAF-1, respectively. Vemurafenib induces cell autophagy.

Regorafenib (BAY 73-4506) is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC₅₀ values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib shows very robust antitumor and antiangiogenic activity.

RMC-7977 is an orally active triple-complex RAS inhibitor that can simultaneously bind to cyclophilin A (CYPA) (K_d = 195 nM) and KRAS (G12V) (K_d = 292 μM). It exhibits broad-spectrum inhibitory activity against KRAS, NRAS, and HRAS proteins and their various wild-type and mutant variants. RMC-7977 induces apoptosis by inhibiting the phosphorylation of ERK, CRAF, and RSK, as well as increasing PARP cleavage. This leads to tumor regression, reduces resistance in KRAS^G12C cancer models, and demonstrates good tolerability across various RAS cancer models.

SB-590885 is a BRAF/c-Raf kinase inhibitor that selectively targets B-Raf, and it amplifies the ERK/MAPK signaling pathway in RAS-activated cells. SB-590885 effectively inhibits the malignant proliferation, transformation and tumorigenicity of oncogenic B-Raf cells; it also induces the proliferation of erythroid progenitor cells, delays their differentiation and promotes hemoglobin synthesis, thereby improving ineffective erythropoiesis and reducing apoptosis. SB-590885 exerts a synergistic effect with TGF-β inhibitors and glucocorticoids, significantly promoting the formation of erythroid colonies in cells from patients with Diamond-Blackfan anemia (DBA). SB-590885 is mainly used in relevant studies on DBA, cisplatin-induced myelosuppression-related anemia, and pan-cancers such as melanoma and colorectal cancer.

Avutometinib (Ro 5126766) is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAF^V600E, CRAF, MEK, and BRAF (IC₅₀: 8.2, 56, 160 nM, and 190 nM, respectively).

Sorafenib (Bay 43-9006) tosylate is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib tosylate induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib tosylate inhibits tumor growth and metastasis in mouse and rat models. Sorafenib tosylate can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

Naporafenib (LXH254) is a potent, selective, orally active, type II BRAF and CRAF inhibitor, with IC₅₀ values of 0.072 and 0.21 nM against CRAF and BRAF, respectively.

LY3009120 (DP-4978) is a pan RAF inhibitor which inhibits BRAF^V600E, BRAF^WT and CRAF^WT with IC₅₀s of 5.8, 9.1 and 15 nM, respectively.

GW 5074 is a potent and selective c-Raf inhibitor with IC₅₀ of 9 nM, and has no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms.

Belvarafenib (HM95573) is a potent and pan RAF (Rapidly Accelerated Fibrosarcoma) inhibitor, with IC₅₀s of 56 nM, 7 nM and 5 nM for B-RAF, B-RAF^v600E and C-RAF respectively.

Dabrafenib Mesylate is a potent and selective Raf kinase inhibitor with IC₅₀s of 0.6 and 5.0 nM for Raf^V600E and c-Raf, respectively.

Agerafenib (CEP-32496; RXDX-105) is a highly potent and orally efficacious inhibitor of BRAF^V600E with a K_d of 14 nM.

AZ 628 is a pan-Raf kinase inhibitor with IC₅₀s of 105, 34 and 29 nM for B-Raf, B-RafV600E, and c-Raf-1, respectively.

Regorafenib (BAY 73-4506) monohydrate is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC₅₀ values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib monohydrate shows very robust antitumor and antiangiogenic activity.

TAK-632 is a potent pan-RAF inhibitor with IC₅₀ of 1.4, 2.4 and 8.3 nM for CRAF, BRAF^V600E, BRAF^WT, respectively.

Raf inhibitor 1 is a potent Raf kinase inhibitor with K_is of 1 nM, 1 nM, and 0.3 nM for B-Raf^WT, B-Raf^V600E, and C-Raf, respectively.

Regorafenib Hydrochloride (BAY 73-4506 hydrochloride) is a multi-target inhibitor for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1 with IC₅₀s of 13/4.2/46, 22, 7, 1.5 and 2.5 nM, respectively.

ZM 336372 is a potent inhibitor of the protein kinase c-Raf. The IC₅₀ value is 0.07 μM in the standard assay, which contains 0.1 mM ATP.