Synonym
BAY-1896953; BAY 1896953; BAY1896953; ORM-15341; ORM 15341; ORM15341; Ketodarolutamide;
IUPAC/Chemical Name
(S)-5-acetyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-3-carboxamide
InChi Key
GMBPVBVTPBWIKC-NSHDSACASA-N
InChi Code
InChI=1S/C19H17ClN6O2/c1-11(22-19(28)18-8-17(12(2)27)23-24-18)10-26-6-5-16(25-26)13-3-4-14(9-21)15(20)7-13/h3-8,11H,10H2,1-2H3,(H,22,28)(H,23,24)/t11-/m0/s1
SMILES Code
ClC1=C(C#N)C=CC(C2=NN(C[C@H](C)NC(C3=NNC(C(C)=O)=C3)=O)C=C2)=C1
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
>2 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
Biological target:
Ketodarolutamide, also known as ORM-15341 and BAY-1896953, is a potent and full antagonist for human AR (hAR) with IC50 = 38 nM.
In vitro activity:
The antagonistic properties of the different compounds in a cell - based transactivation assay using an MMT - driven luciferase reporter were determined. For darolutamide, the (S,R)‐ and (S,S)‐diastereomers, and the main in vivo metabolite keto‐darolutamide, a strong antagonistic activity against AR wild type, when stimulating with 1 nM R1881, was found. This was reduced but still significantly better than observed for other AR antagonists when increasing the androgen level used for stimulation to 10 nM. Strong antagonism was also measured for darolutamide, its diastereomers and for keto‐darolutamide when testing the W742C and W742L forms.
Reference: Int J Cancer. 2019 Sep 1;145(5):1382-1394. https://pubmed.ncbi.nlm.nih.gov/30828788/
In vivo activity:
The absorption, distribution, metabolism and excretion properties of darolutamide in rats are reported. Keto-darolutamide was the most abundant metabolite in rat hepatocytes and the only major one in plasma. Interconversion between diastereoisomers was observed.
Reference: Xenobiotica. 2020 Aug;50(8):967-979. https://pubmed.ncbi.nlm.nih.gov/32003293/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
252.00 |
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
396.84
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.
| 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. Sugawara T, Baumgart SJ, Nevedomskaya E, Reichert K, Steuber H, Lejeune P, Mumberg D, Haendler B. Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models. Int J Cancer. 2019 Sep 1;145(5):1382-1394. doi: 10.1002/ijc.32242. Epub 2019 Mar 23. PMID: 30828788; PMCID: PMC6766977.
2. Taavitsainen P, Gieschen H, Korjamo T, Kähkönen M, Malmström C, Prien O, Niehues M, Sandmann S, Janssen W, Koskinen M. Absorption, distribution, metabolism and excretion of darolutamide (a novel non-steroidal androgen receptor antagonist) in rats. Xenobiotica. 2020
In vitro protocol:
1. Sugawara T, Baumgart SJ, Nevedomskaya E, Reichert K, Steuber H, Lejeune P, Mumberg D, Haendler B. Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models. Int J Cancer. 2019 Sep 1;145(5):1382-1394. doi: 10.1002/ijc.32242. Epub 2019 Mar 23. PMID: 30828788; PMCID: PMC6766977.
In vivo protocol:
1. Taavitsainen P, Gieschen H, Korjamo T, Kähkönen M, Malmström C, Prien O, Niehues M, Sandmann S, Janssen W, Koskinen M. Absorption, distribution, metabolism and excretion of darolutamide (a novel non-steroidal androgen receptor antagonist) in rats. Xenobiotica. 2020
1: Saini NK, Gabani BB, Todmal U, Sulochana SP, Kiran V, Zainuddin M, Balaji N, Polina SB, Srinivas NR, Mullangi R. Pharmacokinetics of Darolutamide in Mouse - Assessment of the Disposition of the Diastereomers, Key Active Metabolite and Interconversion Phenomenon: Implications to Cancer Patients. Drug Metab Lett. 2020 May 20. doi: 10.2174/1872312814666200521091236. Epub ahead of print. PMID: 32436836.
2: Zakkula A, Kiran V, Todmal U, Sulochana SP, Mullangi R. RP-HPLC-UV Method for Simultaneous Quantification of Second Generation Non-Steroidal Antiandrogens Along with their Active Metabolites in Mice Plasma: Application to a Pharmacokinetic Study. Drug Res (Stuttg). 2019 Oct;69(10):537-544. doi: 10.1055/a-0790-8309. Epub 2018 Dec 10. PMID: 30536259.
3: Sulochana SP, Saini NK, Daram P, Polina SB, Mullangi R. Validation of an LC- MS/MS method for simultaneous quantitation of enzalutamide, N-desmethylenzalutamide, apalutamide, darolutamide and ORM-15341 in mice plasma and its application to a mice pharmacokinetic study. J Pharm Biomed Anal. 2018 Jul 15;156:170-180. doi: 10.1016/j.jpba.2018.04.038. Epub 2018 Apr 24. PMID: 29709784.
4: Balaji N, Sulochana SP, Saini NK, A SK, Mullangi R. Validated Chiral LC-ESI- MS/MS Method for the Simultaneous Quantification of Darolutamide Diastereomers and Its Active Metabolite in Mice Plasma: Application to a Pharmacokinetic Study. Drug Res (Stuttg). 2018 Nov;68(11):615-624. doi: 10.1055/a-0580-7218. Epub 2018 Mar 20. PMID: 29558780.
5: Dittakavi S, Nagasuri PKVSP, Sulochana SP, Saim SM, Mallurwar SR, Zainuddin M, Dewang P, Rajagopal S, Mullangi R. LC-MS/MS-ESI method for simultaneous quantification of darolutamide and its active metabolite, ORM-15341 in mice plasma and its application to a pharmacokinetic study. J Pharm Biomed Anal. 2017 Oct 25;145:454-461. doi: 10.1016/j.jpba.2017.06.074. Epub 2017 Jul 13. PMID: 28743076.
