Urothelial Cancer

Trastuzumab vedotin (MRG002; Trastuzumab MMAE) is an antibody-drug conjugate and cytotoxin targeting HER2, with a K_d of 7.50E-11 M for human HER2. After binding to HER2, Trastuzumab vedotin undergoes internalization and lysosomal trafficking, delivering a cytotoxic payload to HER2-expressing cells and inducing tumor regression in in vivo xenograft models with HER2-expressing tumors. The anti-tumor activity of Trastuzumab vedotin is enhanced when used in combination with anti-PD-1 antibodies, and it exhibits preclinical anti-tumor activity in drug-resistant breast cancer, gastric cancer, and urothelial carcinoma PDX models. Trastuzumab vedotin has low antibody-dependent cellular cytotoxicity activity and can be used in studies related to HER2-positive breast cancer, HER2-positive gastric cancer, and unresectable locally advanced or metastatic HER2-positive urothelial carcinoma.

Dabogratinib (TYRA-300) is an orally active, selective FGFR3 inhibitor with an IC₅₀ of 11 nM. Dabogratinib exhibits antitumor activity against urothelial carcinoma and solid tumors. Dabogratinib downregulates the FGFR3 and ERK1/2 signaling pathways, and induces tumor growth inhibition and regression in FGFR3-altered xenograft models. Dabogratinib promotes chondrocyte proliferation and differentiation, drives endochondral bone formation and overall body growth, partially restores long bone proportions, and improves craniofacial and spinal morphology. Dabogratinib can be used for the research of metastatic urothelial carcinoma, achondroplasia and hypochondroplasia.

IMC-D11 (LY-3076226 antibody) is an anti-FGFR3 IgG1 monoclonal antibody with an EC₅₀ of approximately 0.1 nM against hFGFR3b and hFGFR3c. IMC-D11 inhibits the growth of FGFR3-dependent lung adenocarcinoma in mouse models and shows no effect on tumors that do not express FGFR3. IMC-D11 can serve as an ADC Antibody for ADC synthesis, such as LY3076226. IMC-D11 is applicable to research related to urothelial carcinoma, multiple myeloma, lung adenocarcinoma, as well as advanced or metastatic cancers.

LC-MF-4 is an orally active VHL-recruiting FGFR3 PROTAC degrader and hERG potassium channel inhibitor. LC-MF-4 has an IC₅₀ of 16.6 nM against human FGFR3, exhibits inhibitory activity against hERG potassium channels, suppresses the expression of genes related to mitochondrial biogenesis and ATP synthesis, inhibits cancer cell proliferation, and shows significant antitumor activity in mice. LC-MF-4 can be used in the research of bladder cancer, urothelial carcinoma, FGFR3^Y373C mutant cancers, and FGFR3-TACC3 fusion-positive cancers.

Sutantatug (SYS6002 Antibody) is a monoclonal antibody targeting Nectin-4, and serves as the antibody moiety of the ADC CRB-701. Sutantatug is applicable to the research of Nectin-4-positive solid tumors, urothelial carcinoma and cervical cancer. The corresponding isotype control for Sutantatug is Human IgG1 kappa, Isotype Control (HY-P99001).

Dabogratinib (GMP) is the GMP-grade version of Dabogratinib (HY-159642). Dabogratinib (TYRA-300) is an orally active, selective FGFR3 inhibitor with an IC₅₀ of 11 nM. Dabogratinib exhibits antitumor activity against urothelial carcinoma and solid tumors. Dabogratinib downregulates the FGFR3 and ERK1/2 signaling pathways, and induces tumor growth inhibition and regression in FGFR3-altered xenograft models. Dabogratinib promotes chondrocyte proliferation and differentiation, drives endochondral bone formation and overall body growth, partially restores long bone proportions, and improves craniofacial and spinal morphology. Dabogratinib can be used for the research of metastatic urothelial carcinoma, achondroplasia and hypochondroplasia.

MPMS-VA is a highly hydrophilic peptide cleavable linker that can be used for the construction of ADCs. MPMS-VA can be cleaved at the Val-Ala site by lysosomal cathepsin B in tumor cells. MPMS-VA can enhance the hydrophilicity of the antibody-drug conjugate linker-payload system. MPMS-VA improves the plasma stability of relevant ADCs and reduces the systemic release of free payload. MPMS-VA can be applied in research related to solid tumors with co-expression of EGFR/HER2, such as lung cancer, breast cancer, gastric cancer, and urothelial carcinoma.

VWK147 is a second-generation HSP90 C-terminal domain (CTD) inhibitor. VWK147 targets the CTD dimerization interface, prevents HSP90 CTD dimerization, disrupts co-chaperone PPID binding to HSP90 CTD, and inhibits HSP90 chaperone function dependent on dimerization. VWK147 reduces protein levels of HSP90 client proteins ULK1, RIPK1, and CDK4 without inducing a heat shock response. VWK147 induces cell death, including apoptosis, in Cisplatin (HY-17394)-sensitive and -resistant urothelial carcinoma cells. VWK147 induces LC3-II accumulation, inhibits autophagosome-lysosome fusion to block canonical autophagy, and induces non-canonical LC3 lipidation independent of ULK1 and PIK3C3 complexes. VWK147 can be used for the research of urothelial carcinoma.