Elacestrant HCl

• CAS: 1349723-93-8
• Catalog Number: ACM1349723938
• Category: Others
• Molecular Weight: 531.56
• Molecular Formula: C30H40Cl2N2O2
• Description: Elacestrant , also known as RAD1901, is an orally available, selective estrogen receptor degrader (SERD) and selective estrogen receptor modulator (SERM), with potential antineoplastic and estrogen-like activities. Upon oral administration of higher doses of RAD1901, this agent acts as a SERD, which binds to the estrogen receptor (ER) and induces a conformational change that results in the degradation of the receptor. This may inhibit the growth and survival of ER-expressing cancer cells. At lower doses of this agent, RAD1901 acts as a SERM and has estrogen-like effects in certain tissues, which can both reduce hot flashes and protect against bone loss. In addition, RAD1901 is able to cross the blood-brain barrier (BBB).
• Synonyms: RAD1901; RAD-1901; RAD 1901; RAD1901 HCl salt; Elacestrant dihydrochloride; Elacestrant HCl
• IUPAC Name: (R)-6-(2-(ethyl(4-(2-(ethylamino)ethyl)benzyl)amino)-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-ol dihydrochloride
• Canonical SMILES: OC1=CC=C2C[C@H](C3=CC=C(OC)C=C3N(CC4=CC=C(CCNCC)C=C4)CC)CCC2=C1.[H]Cl.[H]Cl
• InChI: InChI=1S/C30H38N2O2.2ClH/c1-4-31-17-16-22-6-8-23(9-7-22)21-32(5-2)30-20-28(34-3)14-15-29(30)26-11-10-25-19-27(33)13-12-24(25)18-26;;/h6-9,12-15,19-20,26,31,33H,4-5,10-11,16-18,21H2,1-3H3;2*1H/t26-;;/m1../s1
• InChI Key: XGFHYCAZOCBCRQ-FBHGDYMESA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1349723-93-8 (HCl); 722533-56-4 (free base)
• Biological Target: Elacestrant dihydrochloride (RAD1901 dihydrochloride) is a selective estrogen receptor degrader (SERD) with IC50s of 48 and 870 nM for ERα and ERβ, respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 67.79; H, 7.59; Cl, 13.34; N, 5.27; O, 6.02
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: With ER and active ER signaling maintained in the CDK4/6i-resistant lines, the relevance of elacestrant treatment in a post-CDK4/6i setting was examined. The sensitive and resistant cell lines were treated with elacestrant, and proliferation was assessed in both a short-term (~ 7 days) and a long-term (3-5 weeks) cell assay. Elacestrant inhibited cell growth of the ESR1wt-CDK4/6i-sensitive and ESR1wt-resistant cells. The EC50 values and the extent of growth inhibition were similar regardless of the sensitivity or prior long-term exposure to each CDK4/6i. The effects of elacestrant on ER and ER signaling in the sensitive and resistant lines were also assessed. Elacestrant degraded ER in the ESR1wt-CDK4/6i sensitive and resistant lines and downregulated GREB1 expression in all these cell lines. RNA sequencing data from the ESR1wt-PalboR cells demonstrated downregulation of additional ER targets, such as EGR3, upon elacestrant treatment Taken together, these data demonstrate the anti-tumor activity of elacestrant in clinically relevant CDK4/6i-resistant models in vitro.; Reference: Breast Cancer Res. 2019 Dec 18;21(1):146. https://pubmed.ncbi.nlm.nih.gov/31852484/
• In Vivo Activity: The antitumor effects of RAD1901 were characterized using an MCF-7 xenograft model in mice supplemented with E2 to stimulate tumor growth. RAD1901 inhibited tumor growth in a dose-dependent manner. Significant TGI responses were seen at doses of 30 and 60 mg/kg RAD1901, with TGI at day 40 being 66% (P<0.05) and 88% (P<0.001), respectively. These were comparable to the TGI observed for tamoxifen and fulvestrant, which on day 40 were 86 and 88%, respectively. RAD1901 was well tolerated, with no adverse effect on body weight. To explore whether higher doses of RAD1901 induced a more robust effect in this model, doses of RAD1901 up to 120 mg/kg were also assessed. RAD1901 inhibition in the 90 and 120 mg/kg groups was significantly greater relative to inhibition by both tamoxifen (P<0.05) and fulvestrant (P<0.05). RAD1901 was well tolerated at these higher dose levels.; Reference: Anticancer Drugs. 2015 Oct;26(9):948-56. https://pubmed.ncbi.nlm.nih.gov/26164151/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).