Tyra-300 99% Shaanxi Dideu Medichem

SURPASS studies are a series of large clinical randomized controlled trials designed to evaluate the efficacy and safety of telpotide in patients with type 2 diabetes mellitus (T2DM). Of these, the head-to-head comparison with Semaglutide SURPASS-2[1] is the most exciting, comparing Tipotide 5mg (n=470), 10mg (n=469), and 15mg (n=469) with semaglutide 1mg (n=468) in glycemic performance. Telpotide reduced HbA1c by an average of 2.0%, 2.2%, and 2.3% compared with baseline HbA1c (8.3%), while semaglutide reduced Hba1c by an average of 1.9%. In terms of weight loss, compared with baseline weight of Chemicalbook (207 pounds), telpotide resulted in average weight loss of 17 pounds, 21 pounds, and 25 pounds, compared with 13 pounds for semaglutide. The experiment showed that tilpotide showed better hypoglycemic and weight loss ability than semaglutide. Another large study enrolled 2,539 adults with at least one obesity complication (excluding diabetes) with a body mass index (BMI) of ≥30kg/m2 or ≥27kg/m2. All subjects were randomly divided into tipotide 5mg, 10mg, 15mg and placebo groups in equal proportion. The results showed that the body weight of each group decreased by 16.1kg, 22.2kg, 23.6kg and 2.4kg, respectively, at 72 weeks [2]. The weight loss effect of tilpotide is comparable to that of weight loss surgery.

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Infigratinib (BGJ398), an FGFR inhibitor, is an ATP-competitive pan-FGFR inhibitor jointly developed by BridgeBio Biopharmaceuticals and LinkoBio. It received FDA approval on May 28, 2021, for the treatment of patients with FGFR2-mutant advanced or metastatic cholangiocarcinoma. With this drug, the FDA has approved three drugs in total; the other two are pemigatinib [FDA/NMPA] and futibatinib [FDA].

Pharmacological Action: Infigratinib selectively binds to and inhibits FGFR activity, blocking downstream signaling cascades and inducing tumor cell death by progressively reducing cancer cell proliferation. It is indicated for the treatment of previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) fusions or other rearrangements as determined by FDA approval in adult patients. This drug was approved by the US FDA on May 21, 2021, and was proposed for inclusion in the Breakthrough Therapy Program by the China National Medical Products Administration on March 28, 2023. Mechanism of Action: Infigratinib exerts its effects at the biochemical and cellular levels by highly selectively inhibiting the activity of FGFR1, FGFR2, FGFR3, and FGFR4. Activation of the FGFR pathway is associated with the proliferation of malignant cancer cells; therefore, inhibition of FGFR-specific kinases can effectively reduce tumor cell proliferation. Uses: BGJ398 is a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinases. Bioactive BGJ398 (NVP-BGJ398) is a potent and selective FGFR inhibitor that acts on FGFR1/2/3 with IC50 values ​​of 0.9 nM/1.4 nM/1 nM. It is more than 40 times more selective for FGFR than for FGFR4 and VEGFR2, and has almost no inhibitory activity against Abl, Fyn, Kit, Lck, Lyn, and Yes.

In vitro studies: BGJ398 inhibited FGFR3-K650E with an IC50 of 4.9 nM. Furthermore, BGJ398 also inhibited VEGFR2. BGJ398 inhibited other kinases, including ABL, FYN, KIT, LCK, LYN, and YES, with IC50 values ​​of 2.3 μM, 1.9 μM, 0.75 μM, 2.5 μM, 0.3 μM, and 1.1 μM, respectively. At the cellular level, BGJ398 inhibited FGFR1-, FGFR2-Q, and FGFR3-dependent BaF3 cell proliferation with IC50 values ​​of 2.9 μM, 2.0 μM, and 2 μM, respectively. BGJ398 interferes with autophosphorylation at specific tyrosine residues, including FGFR-WT, FGFR2-WT, FGFR3-K650E, FGFR3-S249C, and FGFR4-WT, with IC50 values ​​of 4.6 nM, 4.9 nM, 5 nM, 5 nM, and 168 nM, respectively. BGJ398 inhibits the proliferation of cancer cells overexpressing wild-type (WT) FGFR3, such as RT112, RT4, SW780, and JMSU1, with IC50 values ​​of 5 nM, 30 nM, 32 nM, and 15 nM, respectively.