Brain cancer can have a wide variety of symptoms including seizures, sleepiness, confusion, and behavioral changes. Not all brain tumors are cancerous, and benign tumors can result in similar symptoms.
Types of Brain Cancer
Brain tumors are abnormal growths of cells in the brain.
~Although such growths are popularly called brain tumors, not all brain tumors are cancer. Cancer is a term reserved for malignant tumors.
~Malignant tumors can grow and spread aggressively, overpowering healthy cells by taking their space, blood, and nutrients. They can also spread to distant parts of the body. Like all cells of the body, tumor cells need blood and nutrients to survive.
~Tumors that do not invade nearby tissue or spread to distant areas are called benign.
~In general, a benign tumor is less serious than a malignant tumor. But a benign tumor can still cause many problems in the brain by pressing on nearby tissue.
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A novel potent, selective, orally active, and CNS penetrant IDO-1 inhibitor with IC50 of 0.41 uM for hIDO-1; weakly inhibits hTDO-2 with IC50 of 140 uM, and shows no activity against hIDO-2 (>100 uM); shows activity both in the HeLa assay (IC50=1.8 uM) as well as in the LPS/INFγ-stimulated THP1 cells (IC50=1.7 uM), maintains good efficiency in the whole blood assay (IC50=4.7 uM); shown significant antitumor activity in mice and very favorable ADME profile.
Prinomastat (AG3340) is a potent, selective MMP inhibitor with pM affinities for inhibiting gelatinases (MMP-2 and -9, Ki=50-150 pM), MMP-14 and MMP-13; demonstrates broad antitumor activity in a number of tumor models, inhibits glioma invasion or growth of the human malignant glioma cell line U87; also suppresses tumor growth in a malignant glioma tumor model.
Chlorotoxin is a 36-amino acid peptide found in the venom of the deathstalker scorpion (Leiurus quinquestriatus); blocks small-conductance chloride channels.
LB-100 (LB100) is a potent serine/threonine protein phosphatase 2A (PP2A) inhibitor; exhibits inhibitory effect in HCC cell lines Huh-7, HepG2, Hep3B, and SNU-449 with mean IC50 of 10 uM; synergistically enhances the activity of doxorubicin and induces expression of HIF-1α and VEGF; significantly enhances tumor growth inhibition by cisplatin in vivo.
IDH 305 (IDH305) is a potent, selective, brain penetrant mutant IDH1 inhibitor with IC50 of 18 and 28 nM for IDH1 R132H and R132C; exhibits >200 fold selectivity over WT IDH1 (IC50=6.14 uM), and no activtiy against IDH2 mutants; inhibits EGF-independent proliferation of HCT116-IDH1R132H+/- cells with IC50 of 20 nM; exhibits in vivo correlation of 2-HG reduction and efficacy in IDH1 mutant xenograft tumor model.
A potent, selective, brain penetrant dual inhibitor of class I PI3Ks and mTOR with Ki of 2/46/3/10/70 nM for PI3Kα/β/δ/γ/mTOR, respectively; highly selective against a panel of 229 kinases (IC50>1 uM); shows antiproliferative (EC50 =0.3-1.1 uM) in 5 GBM cell lines; significantly and dose-dependently inhibits tumor growth in a subcutaneous U87 tumor xenograft model of glioblastoma in mice.
Sulfatinib (HMPL-012) is a potent, multi-targeted tyrosine kinase inhibitor of VEGFR-1/2/3, FGFR1, CSF1R with IC50 of 2/24/1 nM, 15 nM, 4 nM, respectively; also potently inhibits TrkB and FLT-3 with IC50 of 41 and 67 nM, shows little to no activity against other 278 other kinases (IC50>150 nM); targets tumor angiogenesis and immune modulation, exhibits an acceptable safety profile and encouraging antitumor activity in clinical investigations.
S49076 is a potent, ATP-competitive tyrosine kinase inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 of <20 nM, also potently inhibits the kinase activity of mutated isoforms of MET (D1246N, Y1248D, Y1248H) and FGFR1/2; only inhibits 6% of kinases on a panel of 442 human wild-type and mutated kinases at 100 nM; inhibits the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocks MET-driven migration of lung carcinoma cells, and inhibits colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL; causes tumor growth arrest in bevacizumab-resistant tumors in cancer xenograft models.
PQR309 (Bimiralisib) is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC50 of 33, 451, 661, 708 and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively; also shows potent activity against PI3Kα E542K/E545K/H2047R mutants with IC50 of 63/136/36 nM, shows no significant activity for VPS34 and DNA-PK (IC50>8,000 nM); inhibits cellular phosphorylation of PKB/Akt on Ser473 and ribosomal S6 on Ser235/236 in A2058 melanoma cells with IC50 of 139 and 205 nM, SKOV3 cell growth IC50 is 237 nM; demonstrates efficiency in inhibiting proliferation in tumor cell lines and rat xenograft models.
CYC065 is a derivative of seliciclib and second generation CDK inhibitor that is mainly active on CDK2/5/9; demonstrates cytotoxicity both in MM cell lines sensitive as well as resistant to conventional chemotherapy with IC50 of 0.06-2 uM; blocks cells in the G1 phase and inhibits cell growth specifically in CCNE1-overexpressing USCs; significantly reduces tumour growth in xenografts derived from CCNE1-amplified USCs, shows synergistic effect in vitro and in vivo combined with Taselisib .
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