BAY-2402234

• CAS: 2225819-06-5
• Catalog Number: ACM2225819065
• Category: Inhibitors
• Molecular Weight: 520.84
• Molecular Formula: C21H18ClF5N4O4
• Description: BAY-2402234 is a potent and selective dihydroorotate dehydrogenase (DHODH) inhibitor for the treatment of myeloid malignancies. BAY 2402234 is a selective low-nanomolar inhibitor of human DHODH enzymatic activity. In vitro, it potently inhibits proliferation of AML cell lines in the sub-nanomolar to low-nanomolar range. BAY 2402234 induces differentiation of AML cell lines also in a sub-nanomolar to low-nanomolar range, demonstrating the anticipated mode of action in cellular mechanistic assays. In vivo, BAY 2402234 exhibits strong in vivo anti-tumor efficacy in monotherapy in several subcutaneous and disseminated AML xenografts as well as AML patient-derived xenograft (PDX) models.
• Synonyms: BAY-2402234; BAY 2402234; BAY2402234; Orludodstat; Orludodstatum
• IUPAC Name: (S)-N-(2-chloro-6-fluorophenyl)-4-(4-ethyl-3-(hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-5-fluoro-2-((1,1,1-trifluoropropan-2-yl)oxy)benzamide
• Canonical SMILES: FC1=C(NC(C2=CC(F)=C(N3N=C(CO)N(CC)C3=O)C=C2O[C@@H](C)C(F)(F)F)=O)C(Cl)=CC=C1
• InChI: InChI=1S/C21H18ClF5N4O4/c1-3-30-17(9-32)29-31(20(30)34)15-8-16(35-10(2)21(25,26)27)11(7-14(15)24)19(33)28-18-12(22)5-4-6-13(18)23/h4-8,10,32H,3,9H2,1-2H3,(H,28,33)/t10-/m0/s1
• InChI Key: KNVJMHHAXCPZHF-JTQLQIEISA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: BAY-2402234 is a dihydroorotate dehydrogenase (DHODH) inhibitor with an IC50 of 1.2 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 48.43; H, 3.48; Cl, 6.81; F, 18.24; N, 10.76; O, 12.29
• Exact Mass: 520.0937
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To investigate the effect of BAY 2402234 on AML (acute myeloid leukemia) cell differentiation, the ability of the drug to upregulate the differentiation marker CD11b was assessed in MOLM-13 and HEL cells. In both cell lines, dose-dependent upregulation of CD11b was observed after BAY 2402234 treatment (Fig. 2a, b, Supplementary Fig. 1a), with EC50s of 3.16 nM in MOLM-13 cells and 0.96 nM in HEL cells (Supplementary Table 3). Whether BAY 2402234 induces cell cycle arrest and apoptosis in AML cells was also evaluated. Treatment with the inhibitor dose-dependently slowed cell doubling (Fig. 2e), induced G2-M cell cycle arrest (Fig. 2f) and induced apoptosis (Fig. 2g) of the cells in a dose- and time-dependent manner.; Reference: Leukemia. 2019 Oct;33(10):2403-2415. https://www.nature.com/articles/s41375-019-0461-5
• In Vivo Activity: The anti-tumor activity of BAY 2402234 was evaluated in three systemic AML xenograft models transplanted by tail vein injection. In HL-60 xenografts, treatment with BAY 2402234 nearly doubled the median survival of mice from 13 to 25 days and showed improved efficacy compared to treatment with cytarabine (Fig. 3f). In MV4-11 xenografts, 70% of mice treated with BAY 2402234 were still alive at the study-endpoint (day 46 of treatment) whereas all of the vehicle-treated mice died by day 28 (Fig. 3g). In a disseminated MOLM-13 xenograft model, tumor burden in the peripheral blood, bone marrow and spleens of control and BAY 2402234-treated mice was analyzed after 8 days of treatment. At that time point, over 40% of the peripheral blood cells in the control mice were human HLA-ABC-positive leukemia cells whereas human leukemia cells represented about 4% of circulating cells in the BAY 2402234 treated mice (Supplementary Fig. 4a).; Reference: Leukemia. 2019 Oct;33(10):2403-2415. https://www.nature.com/articles/s41375-019-0461-5
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).