WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205485
CAS#: 183387-50-0
Description: Apoptone, also known as HE3235, is an orally bioavailable adrenal steroid analogue with potential antineoplastic activity. Androstane steroid HE3235 appears to bind the androgen receptor (AR), down-regulating anti-apoptotic genes, such as Bcl-2, while increasing the expression of pro-apoptotic genes, such as caspases. In vitro and in vivo studies indicate that this agent inhibits androstenediol-dependent LNCaP cell tumor growth. In addition, HE3235 may potentiate chemotherapeutic agents by down-regulating ABCG2, the gene encoding the multi-drug resistant (MDR) protein MDR2.
Hodoodo Cat#: H205485
Name: Apoptone
CAS#: 183387-50-0
Chemical Formula: C21H32O2
Exact Mass: 316.24
Molecular Weight: 316.478
Elemental Analysis: C, 79.70; H, 10.19; O, 10.11
Synonym: HE3235, HE-3235, HE3235, Apotone
IUPAC/Chemical Name: (3R,5S,8R,9S,10S,13S,14S,17R)-17-ethynyl-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol
InChi Key: CKAXZOYFIHQCBN-JRRMKBMNSA-N
InChi Code: InChI=1S/C21H32O2/c1-4-21(23)12-9-18-16-6-5-14-13-15(22)7-10-19(14,2)17(16)8-11-20(18,21)3/h1,14-18,22-23H,5-13H2,2-3H3/t14-,15+,16+,17-,18-,19-,20-,21-/m0/s1
SMILES Code: O[C@@H]1CC[C@]2(C)[C@@]3([H])CC[C@]4(C)[C@](O)(C#C)CC[C@@]4([H])[C@]3([H])CC[C@@]2([H])C1
Appearance: Solid powder
Purity: >98%
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: HE3235 is a n orally bioavailable adrenal steroid analogue with potential antineoplastic activity. Androstane steroid HE3235 appears to bind the androgen receptor (AR), down-regulating anti-apoptotic genes, such as Bcl-2, while increasing the expression of pro-apoptotic genes, such as caspases. In vitro and in vivo studies indicate that this agent inhibits androstenediol-dependent LNCaP cell tumor growth. In addition, HE3235 may potentiate chemotherapeutic agents by down-regulating ABCG2, the gene encoding the multi-drug resistant (MDR) protein MDR2. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). Current developer: Harbor Biosciences.
| Biological target: | HE-3235 acts as an androgen receptor antagonist. |
| In vitro activity: | Based on the observations above, the possibility that HE3235 was affecting cell viability in LNCaP cells was examined. Figure 5 shows a modest increase (8–21%) in the percentage of apoptotic LNCaP cells after 4 days of culture with HE3235, suggesting that HE3235 is cytotoxic for LNCaP cells. Reference: Br J Cancer. 2009 Apr 7; 100(7): 1068–1072. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669987/ |
| In vivo activity: | This study set out to investigate whether HE3235 inhibits growth of CaP tumors in castrated male mice in the absence of AED. These experimental conditions mimic the clinical scenario of patients treated with agents aimed at blocking adrenal synthesis of androgens (e.g., ketoconazole). In this setting, HE3235 significantly inhibited the tumor doubling times of LuCaP35V (LuCaP35V + HE3235, 18.2 ± 6.28 days; untreated LuCaP35V, 10.44 ± 1.8 days; P < .0001; Figure 2B). HE3235 treatment resulted in significant increases in serum PSA levels in the treated animals versus control animals bearing LuCaP35V tumors in the period of 1 to 3 weeks after treatment initiation (P < .0001; Figure 2B). Reference: Neoplasia. 2009 Nov; 11(11): 1216–1225. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767223/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 10.0 | 31.60 | |
| DMSO:PBS (pH 7.2) (1:6) | 0.1 | 0.44 | |
| DMF | 10.0 | 31.60 | |
| Ethanol | 10.0 | 31.60 |
The following data is based on the product molecular weight 316.48 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. Koreckij TD, Trauger RJ, Montgomery RB, Pitts TE, Coleman I, Nguyen H, Reading CL, Nelson PS, Vessella RL, Corey E. HE3235 inhibits growth of castration-resistant prostate cancer. Neoplasia. 2009 Nov;11(11):1216-25. doi: 10.1593/neo.09960. PMID: 19881957; PMCID: PMC2767223. 2. Trauger R, Corey E, Bell D, White S, Garsd A, Stickney D, Reading C, Frincke J. Inhibition of androstenediol-dependent LNCaP tumour growth by 17alpha-ethynyl-5alpha-androstane-3alpha, 17beta-diol (HE3235). Br J Cancer. 2009 Apr 7;100(7):1068-72. doi: 10.1038/sj.bjc.6604987. PMID: 19337256; PMCID: PMC2669987. |
| In vitro protocol: | 1. Koreckij TD, Trauger RJ, Montgomery RB, Pitts TE, Coleman I, Nguyen H, Reading CL, Nelson PS, Vessella RL, Corey E. HE3235 inhibits growth of castration-resistant prostate cancer. Neoplasia. 2009 Nov;11(11):1216-25. doi: 10.1593/neo.09960. PMID: 19881957; PMCID: PMC2767223. 2. Trauger R, Corey E, Bell D, White S, Garsd A, Stickney D, Reading C, Frincke J. Inhibition of androstenediol-dependent LNCaP tumour growth by 17alpha-ethynyl-5alpha-androstane-3alpha, 17beta-diol (HE3235). Br J Cancer. 2009 Apr 7;100(7):1068-72. doi: 10.1038/sj.bjc.6604987. PMID: 19337256; PMCID: PMC2669987. |
| In vivo protocol: | 1. Koreckij TD, Trauger RJ, Montgomery RB, Pitts TE, Coleman I, Nguyen H, Reading CL, Nelson PS, Vessella RL, Corey E. HE3235 inhibits growth of castration-resistant prostate cancer. Neoplasia. 2009 Nov;11(11):1216-25. doi: 10.1593/neo.09960. PMID: 19881957; PMCID: PMC2767223. 2. Trauger R, Corey E, Bell D, White S, Garsd A, Stickney D, Reading C, Frincke J. Inhibition of androstenediol-dependent LNCaP tumour growth by 17alpha-ethynyl-5alpha-androstane-3alpha, 17beta-diol (HE3235). Br J Cancer. 2009 Apr 7;100(7):1068-72. doi: 10.1038/sj.bjc.6604987. PMID: 19337256; PMCID: PMC2669987. |
1: Koreckij TD, Trauger RJ, Montgomery RB, Pitts TE, Coleman I, Nguyen H, Reading CL, Nelson PS, Vessella RL, Corey E. HE3235 inhibits growth of castration-resistant prostate cancer. Neoplasia. 2009 Nov;11(11):1216-25. doi: 10.1593/neo.09960. PMID: 19881957; PMCID: PMC2767223.
2: Trauger R, Corey E, Bell D, White S, Garsd A, Stickney D, Reading C, Frincke J. Inhibition of androstenediol-dependent LNCaP tumour growth by 17alpha- ethynyl-5alpha-androstane-3alpha, 17beta-diol (HE3235). Br J Cancer. 2009 Apr 7;100(7):1068-72. doi: 10.1038/sj.bjc.6604987. PMID: 19337256; PMCID: PMC2669987.
3: Ahlem CN, Frincke JM, White SK, Reading CL, Trauger RJ, Lakshmanaswamy R. 17α-ethynyl-5α-androstane-3α, 17β-diol treatment of MNU-induced mammary cancer in rats. Int J Breast Cancer. 2011;2011:618757. doi: 10.4061/2011/618757. Epub 2011 Feb 14. PMID: 22332014; PMCID: PMC3276108.
4: Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J. 17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism. Invest New Drugs. 2012 Feb;30(1):59-78. doi: 10.1007/s10637-010-9517-0. Epub 2010 Sep 3. PMID: 20814732.
5: Colbourn D. Sequencing of cabazitaxel in metastatic castrate-resistant prostate cancer: a case report. Case Rep Oncol. 2012 May;5(2):320-4. doi: 10.1159/000339576. Epub 2012 Jun 21. PMID: 22933996; PMCID: PMC3398088..
