WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206514
CAS#: 1297538-32-9
Description: ODM-201, also known as Darolutamide, is a new-generation, potent and selective androgen receptor (AR) inhibitor which is potential useful for treatment of castration-resistant prostate cancer (CRPC). ODM-201 is a full and high-affinity AR antagonist that, similar to second-generation antiandrogens enzalutamide and ARN-509, inhibits testosterone-induced nuclear translocation of AR. Importantly, ODM-201 also blocks the activity of the tested mutant ARs arising in response to antiandrogen therapies, including the F876L mutation that confers resistance to enzalutamide and ARN-509. In addition, ODM-201 reduces the growth of AR-overexpressing VCaP prostate cancer cells both in vitro and in a castration-resistant VCaP xenograft model. ODM-201 overcomes resistance to AR-targeted therapies by antagonizing both overexpressed and mutated ARs. ODM-201 is currently in a phase 3 trial in CRPC.
Hodoodo Cat#: H206514
Name: ODM-201
CAS#: 1297538-32-9
Chemical Formula: C19H19ClN6O2
Exact Mass: 398.13
Molecular Weight: 398.850
Elemental Analysis: C, 57.22; H, 4.80; Cl, 8.89; N, 21.07; O, 8.02
Synonym: ODM-201; ODM 201; ODM201; Darolutamide; Nubeqa.
IUPAC/Chemical Name: N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide
InChi Key: ANGUXJDGJCHGOG-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H29N5O/c1-19-8-9-22-23(27-19)6-3-7-24(22)29-16-14-28(15-17-29)12-10-20-4-2-5-21(18-20)30-13-11-26-25(30)31/h2-9,18H,10-17H2,1H3,(H,26,31)
SMILES Code: O=C(C1=NNC(C(O)C)=C1)N[C@@H](C)CN2N=C(C3=CC=C(C#N)C(Cl)=C3)C=C2
Appearance: White to off-white 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, not in water
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
More Info:
| Biological target: | Darolutamide (ODM-201, BAY-1841788) is a novel androgen receptor (AR) antagonist that blocks AR nuclear translocation with Ki of 11 nM. |
| In vitro activity: | In competitive AR binding assays, the inhibition constant (Ki) values of Darolutamide (ODM-201) are 11 nM. ODM-201and ORM-15341 suppresse androgen-induced cell proliferation more efficaciously than enzalutamide or ARN-509, IC50 values being 230 and 170 nM for Darolutamide and ORM-15341 vs. 410 and 420 nM for enzalutamide and ARN-509. Darolutamide has no effect on the viability of AR-negative cell lines tested, DU-145 prostate cancer cells and H1581 lung cancer cells confirming that the antiproliferative properties of Darolutamide and ORM-15341 are specific to AR-dependent PC cells. Reference: Sci Rep. 2015 Jul 3;5:12007. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26137992/ |
| In vivo activity: | Darolutamide (ODM-201) showes a significant antitumor activity with both doses, 50 mg/kg twice daily being more efficacious compared to castrated, untreated mice (p |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 256.50 |
The following data is based on the product molecular weight 398.85 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. Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3;5:12007. doi: 10.1038/srep12007. PMID: 26137992; PMCID: PMC4490394. 2. Borgmann H, Lallous N, Ozistanbullu D, Beraldi E, Paul N, Dalal K, Fazli L, Haferkamp A, Lejeune P, Cherkasov A, Gleave ME. Moving Towards Precision Urologic Oncology: Targeting Enzalutamide-resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Novel Inhibitor Darolutamide (ODM-201). Eur Urol. 2018 Jan;73(1):4-8. doi: 10.1016/j.eururo.2017.08.012. Epub 2017 Aug 26. PMID: 28851578. |
| In vitro protocol: | 1. Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3;5:12007. doi: 10.1038/srep12007. PMID: 26137992; PMCID: PMC4490394. 2. Borgmann H, Lallous N, Ozistanbullu D, Beraldi E, Paul N, Dalal K, Fazli L, Haferkamp A, Lejeune P, Cherkasov A, Gleave ME. Moving Towards Precision Urologic Oncology: Targeting Enzalutamide-resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Novel Inhibitor Darolutamide (ODM-201). Eur Urol. 2018 Jan;73(1):4-8. doi: 10.1016/j.eururo.2017.08.012. Epub 2017 Aug 26. PMID: 28851578. |
| In vivo protocol: | 1. Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3;5:12007. doi: 10.1038/srep12007. PMID: 26137992; PMCID: PMC4490394. 2. Borgmann H, Lallous N, Ozistanbullu D, Beraldi E, Paul N, Dalal K, Fazli L, Haferkamp A, Lejeune P, Cherkasov A, Gleave ME. Moving Towards Precision Urologic Oncology: Targeting Enzalutamide-resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Novel Inhibitor Darolutamide (ODM-201). Eur Urol. 2018 Jan;73(1):4-8. doi: 10.1016/j.eururo.2017.08.012. Epub 2017 Aug 26. PMID: 28851578. |
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10: Higano C. Enzalutamide, apalutamide, or darolutamide: are apples or bananas best for patients? Nat Rev Urol. 2019 Jun;16(6):335-336. doi: 10.1038/s41585-019-0186-2. PubMed PMID: 31040439.
11: 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. PubMed PMID: 30828788; PubMed Central PMCID: PMC6766977.
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13: Killock D. ARAMIS - is darolutamide set to become the 'third musketeer' of nmCRPC? Nat Rev Clin Oncol. 2019 May;16(5):273. doi: 10.1038/s41571-019-0191-7. PubMed PMID: 30809027.
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15: Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. doi: 10.1056/NEJMoa1815671. Epub 2019 Feb 14. PubMed PMID: 30763142.
16: Fizazi K, Smith MR, Tombal B. Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. Clin Genitourin Cancer. 2018 Oct;16(5):332-340. doi: 10.1016/j.clgc.2018.07.017. Epub 2018 Jul 24. Review. PubMed PMID: 30197098.
17: 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. PubMed PMID: 29709784.
18: 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. PubMed PMID: 29558780.
19: Balaji N, Sulochana SP, Saini NK, A SK, Mullangi R. Validation of a chiral LC-MS/MS-ESI method for the simultaneous quantification of darolutamide diastereomers in mouse plasma and its application to a stereoselective pharmacokinetic study in mice. Biomed Chromatogr. 2018 May;32(5):e4173. doi: 10.1002/bmc.4173. Epub 2018 Jan 22. PubMed PMID: 29315691.
20: Matsubara N, Mukai H, Hosono A, Onomura M, Sasaki M, Yajima Y, Hashizume K, Yasuda M, Uemura M, Zurth C. Erratum to: Phase 1 study of darolutamide (ODM-201), a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2017 Dec;80(6):1073-1077. doi: 10.1007/s00280-017-3433-3. PubMed PMID: 29063294; PubMed Central PMCID: PMC6828099.
Wei J, Yin L, Li J, Wang J, Pu T, Duan P, Lin TP, Gao AC, Wu BJ. Bidirectional Cross-talk between MAOA and AR Promotes Hormone-Dependent and Castration-Resistant Prostate Cancer. Cancer Res. 2021 Aug 15;81(16):4275-4289. doi: 10.1158/0008-5472.CAN-21-0198. Epub 2021 Jun 24. PMID: 34167949; PMCID: PMC8373824.
