Orteronel | TAK-700 | CAS#426219-18-3 | 566939-85-3 | CYP17 inhibitor

MedKoo Cat#: 200724 | Name: Orteronel

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Description:

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

Orterone, also known as TAK-700, is an orally bioavailable non-steroidal androgen synthesis inhibitor of steroid 17alpha-monooxygenase (17,20 lyase) with potential antiandrogen activity. TAK-700 binds to and inhibits the steroid 17alpha-monooxygenase in both the testes and adrenal glands, thereby inhibiting androgen production. This may decrease androgen-dependent growth signaling and may inhibit cell proliferation of androgen-dependent tumor cells. Orteronel is a CYP17 inhibitor.

Chemical Structure

Orteronel

CAS#566939-85-3 (s-isomer)

Theoretical Analysis

MedKoo Cat#: 200724

Name: Orteronel

CAS#: 566939-85-3 (s-isomer)

Chemical Formula: C18H17N3O2

Exact Mass: 307.1321

Molecular Weight: 307.35

Elemental Analysis: C, 70.34; H, 5.58; N, 13.67; O, 10.41

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 300.00	2 weeks
10mg	USD 550.00	2 weeks

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Related CAS #

426219-18-3 (racemic) 566939-85-3 (s-isomer)

Synonym

TAK700; TAK-700; TAK 700; Orteronel

IUPAC/Chemical Name

(S)-6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide

InChi Key

OZPFIJIOIVJZMN-SFHVURJKSA-N

InChi Code

InChI=1S/C18H17N3O2/c1-19-17(22)14-3-2-13-9-15(5-4-12(13)8-14)18(23)6-7-21-11-20-10-16(18)21/h2-5,8-11,23H,6-7H2,1H3,(H,19,22)/t18-/m0/s1

SMILES Code

O=C(NC)C1=CC=C2C=C([C@@]3(O)CCN4C=NC=C43)C=CC2=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, not in water

Shelf Life

>5 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

Related CAS# 426219-18-3 (Orteronel, racemic mixture) 566939-85-3 (Orteronel, S-isomer)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8S03C21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Orteronel (TAK-700) is a highly selective inhibitor of human 17,20-lyase (CYP17) with IC50 of 38 nM.

In vitro activity:

In terms of human CYP17A1 and human adrenal tumor cells, orteronel inhibited 17,20-lyase activity 5.4 times more potently than 17-hydroxylase activity in cell-free enzyme assays and DHEA production 27 times more potently than cortisol production in human adrenal tumor cells, suggesting greater specificity of inhibition between 17,20-lyase and 17-hydroxylase activities in humans vs monkeys. Reference: J Steroid Biochem Mol Biol. 2012 Apr;129(3-5):115-28. https://pubmed.ncbi.nlm.nih.gov/22249003/

In vivo activity:

The specific decline of serum estradiol and androgen levels in hypophysectomized female rats by orteronel in comparison with aromatase inhibitor anastrozole was evaluated; orteronel at doses ≥3mg/kg significantly suppressed serum estradiol, testosterone, androstenedione and 17-hydroxyprogesterone levels, and increased progesterone levels in the estrogen-synthesis pathway. Orteronel at 15mg/kg/day (7.5mg/kg/treatment, twice daily [bid]) continued to suppress the estradiol surge prior to the start of luteal phase for 1.5-times the average duration of three consecutive, pre-treatment menstrual cycles, while serum progesterone was maintained at levels almost equal to those in the luteal phase although a certain portion of this increased level of progesterone could be of adrenal-origin. Reference: J Steroid Biochem Mol Biol. 2013 Nov;138:298-306. https://pubmed.ncbi.nlm.nih.gov/23856460/

	Solvent	mg/mL	mM
Solubility
	DMF	10.0	32.54
	DMSO	12.2	39.51
	Ethanol	0.2	0.65

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 307.35 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. Yamaoka M, Hara T, Hitaka T, Kaku T, Takeuchi T, Takahashi J, Asahi S, Miki H, Tasaka A, Kusaka M. Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J Steroid Biochem Mol Biol. 2012 Apr;129(3-5):115-28. doi: 10.1016/j.jsbmb.2012.01.001. Epub 2012 Jan 12. PMID: 22249003.

In vitro protocol:

In vivo protocol:

1: Gebrael G, Jo Y, Swami U, Plets M, Hage Chehade C, Narang A, Gupta S, Myint ZW, Sayegh N, Tangen CM, Hussain M, Dorff T, Lara PN Jr, Lerner SP, Thompson I, Agarwal N. Bone Pain and Survival Among Patients With Metastatic, Hormone- Sensitive Prostate Cancer: A Secondary Analysis of the SWOG-1216 Trial. JAMA Netw Open. 2024 Jul 1;7(7):e2419966. doi: 10.1001/jamanetworkopen.2024.19966. PMID: 38980676; PMCID: PMC11234233. 2: Parikh M, Tangen C, Hussain MHA, Gupta S, Callis S, Jo Y, Harzstark A, Paller CJ, George S, Zibelman MR, Cheng HH, Maughan BL, Zhang J, Pachynski RK, Bryce AH, Lin DW, Quinn DI, Lerner SP, Thompson IM, Dorff TB, Lara PN, Agarwal N. Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide. Eur Urol Oncol. 2024 Mar 23:S2588-9311(24)00054-3. doi: 10.1016/j.euo.2024.03.001. Epub ahead of print. PMID: 38523017. 3: Lara PN Jr, Mayerson E, Gertz E, Tangen C, Goldkorn A, van Loan M, Hussain M, Gupta S, Zhang J, Parikh M, Twardowski P, Quinn DI, LeBlanc M, Thompson I, Agarwal N. Markers of bone metabolism and overall survival in men with bone- metastatic hormone sensitive prostate cancer (HSPC): A subset analysis of SWOG S1216, a phase III trial of androgen deprivation with or without orteronel. Prostate Cancer Prostatic Dis. 2024 Feb 29. doi: 10.1038/s41391-024-00813-3. Epub ahead of print. PMID: 38424319. 4: Lee YS, Kim SH, Tae JH, Chang IH, Kim TH, Myung SC, Kim M, Nguyen TT, Choi J, Kim JH, Kim JW, Choi SY. Oral chemotherapeutic agents in metastatic hormone- sensitive prostate cancer: A network meta-analysis of randomized controlled trials. Prostate Int. 2023 Sep;11(3):159-166. doi: 10.1016/j.prnil.2023.06.003. Epub 2023 Jul 4. PMID: 37745904; PMCID: PMC10513908. 5: Sayegh N, Swami U, Jo Y, Gebrael G, Haaland B, Gupta S, Plets M, Hussain MHA, Quinn DI, Lara PN Jr, Thompson IM Jr, Agarwal N. Race and Treatment Outcomes in Patients With Metastatic Castration-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG 1216 Phase 3 Trial. JAMA Netw Open. 2023 Aug 1;6(8):e2326546. doi: 10.1001/jamanetworkopen.2023.26546. PMID: 37526936; PMCID: PMC10394570. 6: Lara PN Jr, Mayerson E, Gertz E, Tangen C, Goldkorn A, van Loan M, Hussain M, Gupta S, Zhang J, Parikh M, Twardowski P, Quinn DI, LeBlanc M, Vogelzang NJ, Thompson I, Agarwal N. Bone Biomarkers and Subsequent Survival in Men with Hormone-sensitive Prostate Cancer: Results from the SWOG S1216 Phase 3 Trial of Androgen Deprivation Therapy with or Without Orteronel. Eur Urol. 2024 Feb;85(2):171-176. doi: 10.1016/j.eururo.2023.03.036. Epub 2023 Apr 19. PMID: 37085425; PMCID: PMC10662935. 7: Joshi BP, Bhandare VV, Vankawala M, Patel P, Patel R, Vyas B, Krishnamurty R. Friedelin, a novel inhibitor of CYP17A1 in prostate cancer from Cassia tora. J Biomol Struct Dyn. 2023 Nov;41(19):9695-9720. doi: 10.1080/07391102.2022.2145497. Epub 2022 Nov 14. PMID: 36373336. 8: Agarwal N, Tangen CM, Hussain MHA, Gupta S, Plets M, Lara PN, Harzstark AL, Twardowski PW, Paller CJ, Zylla D, Zibelman MR, Levine E, Roth BJ, Goldkorn A, Vaena DA, Kohli M, Crispino T, Vogelzang NJ, Thompson IM Jr, Quinn DI. Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216). J Clin Oncol. 2022 Oct 1;40(28):3301-3309. doi: 10.1200/JCO.21.02517. Epub 2022 Apr 21. PMID: 35446628; PMCID: PMC9553390. 9: Chen MK, Liang ZJ, Luo DS, Xue KY, Liao DY, Li Z, Yu Y, Chen ZS, Zhao SC. Abiraterone, Orteronel, Enzalutamide and Docetaxel: Sequential or Combined Therapy? Front Pharmacol. 2022 Feb 17;13:843110. doi: 10.3389/fphar.2022.843110. PMID: 35250590; PMCID: PMC8891580. 10: Yardley DA, Young RR, Adelson KB, Silber AL, Najera JE, Daniel DB, Peacock N, Finney L, Hoekstra SJ, Shastry M, Hainsworth JD, Burris HA. A Phase II Study Evaluating Orteronel, an Inhibitor of Androgen Biosynthesis, in Patients With Androgen Receptor (AR)-Expressing Metastatic Breast Cancer (MBC). Clin Breast Cancer. 2022 Apr;22(3):269-278. doi: 10.1016/j.clbc.2021.10.011. Epub 2021 Oct 28. PMID: 34824002. 11: Guengerich FP, McCarty KD, Chapman JG, Tateishi Y. Stepwise binding of inhibitors to human cytochrome P450 17A1 and rapid kinetics of inhibition of androgen biosynthesis. J Biol Chem. 2021 Aug;297(2):100969. doi: 10.1016/j.jbc.2021.100969. Epub 2021 Jul 15. PMID: 34273352; PMCID: PMC8350020. 12: Goldkorn A, Tangen C, Plets M, Morrison GJ, Cunha A, Xu T, Pinski JK, Ingles SA, Triche T, Harzstark AL, Kohli M, MacVicar GR, Vaena DA, Crispino AW, McConkey DJ, Lara PN Jr, Hussain MHA, Quinn DI, Vogelzang NJ, Thompson IM Jr, Agarwal N. Baseline Circulating Tumor Cell Count as a Prognostic Marker of PSA Response and Disease Progression in Metastatic Castrate-Sensitive Prostate Cancer (SWOG S1216). Clin Cancer Res. 2021 Apr 1;27(7):1967-1973. doi: 10.1158/1078-0432.CCR-20-3587. Epub 2021 Jan 26. PMID: 33500355; PMCID: PMC8026618. 13: Cao Q, Bai P, Shi D, Liao J, Shi H, Xing Y, Chen K, Zhang X. CYP17 inhibitors improve the prognosis of metastatic castration-resistant prostate cancer patients: A meta-analysis of published trials. J Cancer Res Ther. 2020 Sep;16(5):990-1001. doi: 10.4103/jcrt.JCRT_295_18. PMID: 33004739. 14: Child SA, Guengerich FP. Multistep Binding of the Non-Steroidal Inhibitors Orteronel and Seviteronel to Human Cytochrome P450 17A1 and Relevance to Inhibition of Enzyme Activity. J Med Chem. 2020 Jun 25;63(12):6513-6522. doi: 10.1021/acs.jmedchem.9b01849. Epub 2020 Apr 9. PMID: 32223238; PMCID: PMC7875674. 15: Guengerich FP, Wilkey CJ, Glass SM, Reddish MJ. Conformational selection dominates binding of steroids to human cytochrome P450 17A1. J Biol Chem. 2019 Jun 28;294(26):10028-10041. doi: 10.1074/jbc.RA119.008860. Epub 2019 May 9. PMID: 31072872; PMCID: PMC6664176. 16: Moll JM, Kumagai J, van Royen ME, Teubel WJ, van Soest RJ, French PJ, Homma Y, Jenster G, de Wit R, van Weerden WM. A bypass mechanism of abiraterone- resistant prostate cancer: Accumulating CYP17A1 substrates activate androgen receptor signaling. Prostate. 2019 Jun;79(9):937-948. doi: 10.1002/pros.23799. Epub 2019 Apr 24. PMID: 31017696; PMCID: PMC6593470. 17: Roviello G, Corona SP, Aieta M, Roudi R. Influence of Age and the Gleason Score in the Choice of Novel Hormonal Therapies Before and After Chemotherapy. Cancer Biother Radiopharm. 2019 Apr;34(3):141-146. doi: 10.1089/cbr.2018.2702. Epub 2019 Jan 8. PMID: 30620216. 18: Weisman AJ, Harmon SA, Perk TG, Eickhoff J, Choyke PL, Kurdziel KA, Dahut WL, Humm JL, Apolo AB, Larson SM, Morris MJ, Perlman SB, Liu G, Jeraj R. Quantification of bone flare on 18F-NaF PET/CT in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2019 May;22(2):324-330. doi: 10.1038/s41391-018-0110-5. Epub 2018 Nov 9. PMID: 30413807; PMCID: PMC7490782. 19: Brown LC, Sonpavde G, Armstrong AJ. Can RECIST response predict success in phase 3 trials in men with metastatic castration-resistant prostate cancer? Prostate Cancer Prostatic Dis. 2018 Sep;21(3):419-430. doi: 10.1038/s41391-018-0049-6. Epub 2018 Jun 1. PMID: 29858595. 20: Roviello G, Generali D. Is the fatigue an adverse event of the second generation of hormonal therapy? Data from a literature-based meta-analysis. Med Oncol. 2018 Jan 31;35(3):29. doi: 10.1007/s12032-018-1081-z. PMID: 29387974.