Cancer is a disease in which cells in the body grow out of control. When cancer starts in the colon or rectum, it is called colorectal cancer. Sometimes it is called Colon cancer, for short.
Colorectal cancer affects men and women of all racial and ethnic groups, and is most often found in people who are 50 years old or older.
Of cancers that affect both men and women, colorectal cancer is the second leading cancer killer in the United States, but it doesn’t have to be. Colorectal cancer screening saves lives. Screening can find precancerous polyps—abnormal growths in the colon or rectum—that can be removed before they turn into cancer. Screening also helps find colorectal cancer at an early stage, when treatment works best. About nine out of every 10 people whose colorectal cancers are found early and treated appropriately are still alive five years later.
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The first orally available, small-molecule TNIK inhibitor with IC50 of 21 nM; also weakly inhibits FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK (IC80>0.1 uM); induces faster migration of TCF4 phosphorylated by TNIK at 0.1-0.3 uM, and completely inhibits at 3 uM; also reduces the expression of TNIK, AXIN2, cMYC, LRP6 and LRP5; abrogates colorectal cancer stemness, suppresses Wnt-driven intestinal tumorigenesis in Apc(min/+) mice.
ML-264 (ML 264) is a potent, selective of KLF5 expression inhibtor, withour effect on kinases associated with the KLF5 pathway; inhibits the proliferation of DLD-1 cells with IC50 of 29 nM, and several other KLF5-expressing cell types as well HCT116, IC50 560 nM; HT29, IC50=130 nM; SW620, IC50=430 nM); potently inhibits proliferation of colorectal cancer cells in vitro through modifications of the cell-cycle profile; efficiently inhibits growth of the tumo in an established xenograft mouse model of colon cancer.
BGB-283 (Lifirafenib, BGB283) is a potent pan RAF inhibitor of BRAF V600E, wt BRAF, CRAFY340/341D and wt ARAF (IC50=5-40 nM); inhibits recombinant BRAFV600E with IC50 of 23 nM; also inhibits EGFR and EGFR T790M/L858R with IC50 of 29 nM and 495 nM respectively; potently inhibits BRAF(V600E)-activated ERK phosphorylation and cell proliferation in vitro; shows tumor growth inhibition in both cell line-derived and primary human colorectal tumor xenografts bearing BRAF(V600E) mutation.
A potent and highly selective small molecule inhibitor of VEGFR1/2/3 with IC50 of 33/3/5/0.5 nM, respectively; weakly inhibits RET, FGFR-1 and c-kit kinases; demonstrates potent inhibition on VEGF-A dependent KDR phosphorylation in HEK293-KDR cells and VEGF-A induced proliferation in primary HUVECs with IC50 of 0.6 nM and 1.7 nM, respectively; suppresses tumor growth inhibition in a panel of tumor xenograft and patient derive xenograft models in mouse; orally active.
Anlotinib (AL-3818) is a novel multi-target tyrosine kinase that primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret; shows antitumor activity against tumor cells carrying mutations in PDGFR α, c-Kit, Met, and epidermal growth factor receptor (EGFR).
A potent multikinase inhibitor that potently inhibits these endothelial cell kinases in biochemical and cellular kinase phosphorylation assays with nanomolar range (IC50=3-200 nM); inhibits VEGFR1/2/3, PDGFRβ, FGFR1, KIT, RET and B-RAF etc.; exhibits potent dose-dependent TGI in various preclinical human xenograft models in mice; orally active.
An inhibitor of Heat shock protein (HSP) synthesis that dose-dependently inhibits the acquisition of thermotolerance and the induction of various HSPs including HSP105, HSP70, and HSP40 in human colon carcinoma cells; inhibits the acquisition of thermotolerance as developed by sodium arsenite, also inhibited at mRNA levels; shows no antitumor effects and does not increase the thermosensitivity of nontolerant tumors in vivo (up to 200 mg/kg).
Regorafenib hydrochloride (BAY73-4506) is a potent, orally active multikinase inhibitor that potently inhibits endothelial cell kinases in biochemical and cellular kinase phosphorylation assays with nanomolar range (IC50=3-200 nM); inhibits VEGFR1/2/3, PDGFRβ, FGFR1, KIT, RET and B-RAF etc.; exhibits potent dose-dependent TGI in various preclinical human xenograft models in mice.
Simurosertib(TAK931;TAK-931) is a potent, selective, ATP competitive and orally bioavailable inhibitor of Cdc7 with IC50 of <0.3 nM; prevents the initiation of DNA replication during mitosis, which causes cell cycle arrest and induces apoptosis, demonstrates antiproliferative activity with cancer cell lines and tumor growth inhibition (TGI) in murine ectopic xenograft models.
Linifanib is a potent multi-RTKs inhibitor of members of VEGFR and PDGFR families with IC50 of 4/3/3/14/4/66/190/170 nM for KDR/FLT1/CSF1R/KIT/FLT3/PDGFRβ/FLT4/Tie2, respectively; much less active (IC50>10 uM) against other nonrelated tyrosine kinases, such as steroid receptor coactivator and EGFR; inhibits RTK phosphorylation (IC50=2, 4, and 7 nM for PDGFRβ, KDR, and CSF-1R, respectively) and VEGF-stimulated proliferation (IC50=0.2 nM for human endothelial cells); exhibits efficacy in human fibrosarcoma and breast, colon, and small cell lung carcinoma xenograft models (ED50=1.5-5 mg/kg, twice daily).
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