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MedKoo Cat#: 207035 | Name: BAY-2402234
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Orludodstat, also known as 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.

Chemical Structure

BAY-2402234
BAY-2402234
CAS#2225819-06-5

Theoretical Analysis

MedKoo Cat#: 207035

Name: BAY-2402234

CAS#: 2225819-06-5

Chemical Formula: C21H18ClF5N4O4

Exact Mass: 520.0937

Molecular Weight: 520.84

Elemental Analysis: C, 48.43; H, 3.48; Cl, 6.81; F, 18.24; N, 10.76; O, 12.29

Price and Availability

Size Price Availability Quantity
5mg USD 250.00 Ready to ship
10mg USD 450.00 Ready to ship
25mg USD 950.00 Ready to ship
50mg USD 1,650.00 Ready to ship
100mg USD 2,950.00 Ready to ship
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Related CAS #
No Data
Synonym
BAY-2402234; BAY 2402234; BAY2402234; Orludodstat;
IUPAC/Chemical 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
InChi Key
KNVJMHHAXCPZHF-JTQLQIEISA-N
InChi Code
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
SMILES Code
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
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
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.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
BAY-2402234 is a dihydroorotate dehydrogenase (DHODH) inhibitor with an IC50 of 1.2 nM.
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
Solvent mg/mL mM
Solubility
DMF 10.0 19.20
DMSO 78.3 150.39
Ethanol 31.5 60.48
Ethanol:PBS (pH 7.2) (1:3) 0.3 0.48
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 520.84 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Christian S, Merz C, Evans L, Gradl S, Seidel H, Friberg A, Eheim A, Lejeune P, Brzezinka K, Zimmermann K, Ferrara S, Meyer H, Lesche R, Stoeckigt D, Bauser M, Haegebarth A, Sykes DB, Scadden DT, Losman JA, Janzer A. The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies. Leukemia. 2019 Oct;33(10):2403-2415. doi: 10.1038/s41375-019-0461-5. Epub 2019 Apr 2. PMID: 30940908.
In vitro protocol:
1. Christian S, Merz C, Evans L, Gradl S, Seidel H, Friberg A, Eheim A, Lejeune P, Brzezinka K, Zimmermann K, Ferrara S, Meyer H, Lesche R, Stoeckigt D, Bauser M, Haegebarth A, Sykes DB, Scadden DT, Losman JA, Janzer A. The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies. Leukemia. 2019 Oct;33(10):2403-2415. doi: 10.1038/s41375-019-0461-5. Epub 2019 Apr 2. PMID: 30940908.
In vivo protocol:
1. Christian S, Merz C, Evans L, Gradl S, Seidel H, Friberg A, Eheim A, Lejeune P, Brzezinka K, Zimmermann K, Ferrara S, Meyer H, Lesche R, Stoeckigt D, Bauser M, Haegebarth A, Sykes DB, Scadden DT, Losman JA, Janzer A. The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies. Leukemia. 2019 Oct;33(10):2403-2415. doi: 10.1038/s41375-019-0461-5. Epub 2019 Apr 2. PMID: 30940908.
1: Shi DD, Savani MR, Levitt MM, Wang AC, Endress JE, Bird CE, Buehler J, Stopka SA, Regan MS, Lin YF, Puliyappadamba VT, Gao W, Khanal J, Evans L, Lee JH, Guo L, Xiao Y, Xu M, Huang B, Jennings RB, Bonal DM, Martin-Sandoval MS, Dang T, Gattie LC, Cameron AB, Lee S, Asara JM, Kornblum HI, Mak TW, Looper RE, Nguyen QD, Signoretti S, Gradl S, Sutter A, Jeffers M, Janzer A, Lehrman MA, Zacharias LG, Mathews TP, Losman JA, Richardson TE, Cahill DP, DeBerardinis RJ, Ligon KL, Xu L, Ly P, Agar NYR, Abdullah KG, Harris IS, Kaelin WG Jr, McBrayer SK. De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma. Cancer Cell. 2022 Sep 12;40(9):939-956.e16. doi: 10.1016/j.ccell.2022.07.011. Epub 2022 Aug 18. PMID: 35985343; PMCID: PMC9515386. 2: Jones SW, Penman SL, French NS, Park BK, Chadwick AE. Investigating dihydroorotate dehydrogenase inhibitor mediated mitochondrial dysfunction in hepatic in vitro models. Toxicol In Vitro. 2021 Apr;72:105096. doi: 10.1016/j.tiv.2021.105096. Epub 2021 Jan 16. PMID: 33460737. 3: Christian S, Merz C, Evans L, Gradl S, Seidel H, Friberg A, Eheim A, Lejeune P, Brzezinka K, Zimmermann K, Ferrara S, Meyer H, Lesche R, Stoeckigt D, Bauser M, Haegebarth A, Sykes DB, Scadden DT, Losman JA, Janzer A. The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies. Leukemia. 2019 Oct;33(10):2403-2415. doi: 10.1038/s41375-019-0461-5. Epub 2019 Apr 2. PMID: 30940908.