Cariprazine free base

• CAS: 839712-12-8
• Catalog Number: ACM839712128
• Category: Others
• Molecular Weight: 427.41
• Molecular Formula: C21H32Cl2N4O
• Description: Cariprazine, also known as RGH-188 and MP-214, is an antipsychotic drug received FDA approval on September 17, 2015. Cariprazine acts as a D2 and D3 receptor partial agonist, with high selectivity towards the D3 receptor. Action on the dopaminergic systems makes it also potentially useful as an add-on therapy in major depressive disorder. Cariprazine is approved for schizophrenia and bipolar disorder. It has also been investigated as a potential adjunct in treatment-resistant major depressive disorder.
• Synonyms: Cariprazine free base; RGH-188; RGH188; RGH 188; MP-214; MP 214; MP214
• IUPAC Name: 3-((1r,4r)-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea
• Canonical SMILES: O=C(N[C@H]1CC[C@H](CCN2CCN(C3=CC=CC(Cl)=C3Cl)CC2)CC1)N(C)C
• InChI: InChI=1S/C21H32Cl2N4O/c1-25(2)21(28)24-17-8-6-16(7-9-17)10-11-26-12-14-27(15-13-26)19-5-3-4-18(22)20(19)23/h3-5,16-17H,6-15H2,1-2H3,(H,24,28)/t16-,17-
• InChI Key: KPWSJANDNDDRMB-QAQDUYKDSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 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: 1083076-69-0 (HCl); 839712-12-8 (free base)
• Biological Target: Cariprazine is a novel antipsychotic drug candidate that exhibits high affinity for the D3 (Ki=0.085 nM) and D2 (Ki=0.49 nM) receptors, and moderate affinity for the 5-HT1A receptor (Ki=2.6 nM).
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 59.01; H, 7.55; Cl, 16.59; N, 13.11; O, 3.74
• Exact Mass: 426.1953
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: Cariprazine had lower affinity at human and rat hippocampal 5-HT(1A) receptors (pK(i) 8.59 and 8.34, respectively) and demonstrated low intrinsic efficacy. Cariprazine displayed low affinity at human 5-HT(2A) receptors (pK(i) 7.73). Moderate or low affinity for histamine H(1) and 5-HT(2C) receptors (pK(i) 7.63 and 6.87, respectively) suggest cariprazine's reduced propensity for adverse events related to these receptors. Cariprazine demonstrated different functional profiles at dopamine receptors depending on the assay system. It displayed D(2) and D(3) antagonism in [(35)S]GTPgammaS binding assays, but stimulated inositol phosphate (IP) production (pEC(50) 8.50, E(max) 30%) and antagonized (+/-)-quinpirole-induced IP accumulation (pK(b) 9.22) in murine cells expressing human D(2L) receptors. It had partial agonist activity (pEC(50) 8.58, E(max) 71%) by inhibiting cAMP accumulation in Chinese hamster ovary cells expressing human D(3) receptors and potently antagonized R(+)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphtalene HBr (7-OH-DPAT)-induced suppression of cAMP formation (pK(b) 9.57). In these functional assays, cariprazine showed similar (D(2)) or higher (D(3)) antagonist-partial agonist affinity and greater (3- to 10-fold) D(3) versus D(2) selectivity compared with aripiprazole.; Reference: J Pharmacol Exp Ther. 2010 Apr;333(1):328-40. https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20093397
• In Vivo Activity: Cariprazine was tested in vivo for antimanic-like activity, using the ouabain-induced hyperactivity model in rats. Cariprazine was more potent than aripiprazole in inhibiting isoproterenol-induced cAMP although both compounds showed similar maximum efficacy. In assays of D2R/β-arrestin 2-dependent interactions, cariprazine showed very weak partial agonist activity, unless the levels of receptor kinase were increased; as an antagonist it showed similar potency to haloperidol and ~fivefold greater potency than aripiprazole. In an animal model of mania, cariprazine showed similar efficacy as lithium in attenuating the effects of ouabain-induced hyperactivity. In summary, the differential effects of cariprazine on D2R G protein and β-arrestin 2 mediators of signal transduction pathways could contribute to its potent antimanic-like activity.; Reference: Pharmacol Res Perspect. 2015 Feb;3(1):e00073. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25692006/
• 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).