Synonym
CGP-62221; CGP 62221; CGP62221; O-Desmethyl PKC412; O-Desmethyl PKC 412; O-Desmethyl PKC-412
IUPAC/Chemical Name
N-((5S,6R,7R,9R)-6-hydroxy-5-methyl-14-oxo-6,7,8,9,15,16-hexahydro-5H,14H-17-oxa-4b,9a,15-triaza-5,9-methanodibenzo[b,h]cyclonona[jkl]cyclopenta[e]-as-indacen-7-yl)-N-methylbenzamide
InChi Key
PXOCRDZEEXVZQC-AFUPZKSLSA-N
InChi Code
InChI=1S/C34H28N4O4/c1-34-31(39)24(36(2)33(41)18-10-4-3-5-11-18)16-25(42-34)37-22-14-8-6-12-19(22)27-28-21(17-35-32(28)40)26-20-13-7-9-15-23(20)38(34)30(26)29(27)37/h3-15,24-25,31,39H,16-17H2,1-2H3,(H,35,40)/t24-,25-,31-,34+/m1/s1
SMILES Code
O=C(N([C@H]1[C@@H](O)[C@@](O2)(C)N3C4=CC=CC=C4C5=C3C6=C(C7=CC=CC=C7N6[C@@]2([H])C1)C8=C5CNC8=O)C)C9=CC=CC=C9
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
Shelf Life
>3 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
Biological target:
CGP71683 hydrochloride is a competitive neuropeptide Y5 receptor antagonist with a Ki of 1.3 nM, and shows no obvious activity at Y1 receptor (Ki, >4000 nM) and Y2 receptor (Ki, 200 nM) in cell membranes.
In vitro activity:
CGP71683 hydrochloride is a competitive neuropeptide Y5 receptor antagonist with a Ki of 1.3 nM, and shows no obvious activity at Y1 receptor (Ki, >4000 nM) and Y2 receptor (Ki, 200 nM) in cell membranes.
Reference: Br J Pharmacol. 2002 Apr;135(8):2029-37. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/11959807/
In vivo activity:
Fed and fasting rats received twice daily central injections (3rd ventricle) of Y5 receptor antagonist (CGP71683; 15nmol/rat) for 72h. Fasted rats also received a single central injection of CGP71683 (15nmol/rat) at the end of 72h of fasting. In fed rats, Y5 receptor blockade reduced total food intake by 32% and body mass by almost 10% (p<0.01), corroborating the role of this receptor in food intake control. 72h-fasted rats exhibited a 4-fold increase in serum TSH (p<0.001), 1h after a single injection of Y5 antagonist. Also with multiple injections during 72h of fasting, Y5 blockade resulted in activation of thyroid axis, as demonstrated by a 3-times rise in serum T4 (p<0.001), accompanied by unchanged TSH and T3. In fed rats, the chronic central administration of CGP71683 resulted in reduced total serum T4 without changes in free T4 and TSH. Serum leptin and PYY were not altered by the NPY central blockade in both fed and fasted rats, suggesting no role of these hormones in the alterations observed. Therefore, the inhibition of central Y5 neurotransmission resulted in activation of thyroid axis during fasting suggesting that NPY-Y5 receptors contribute to fasting-induced TSH and TH suppression.
Reference: Regul Pept. 2011 Nov 10;171(1-3):43-7. https://linkinghub.elsevier.com/retrieve/pii/S0167-0115(11)00132-7
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
160.0 |
312.46 |
|
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
556.62
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 |
In vitro protocol:
1. Lecklin A, Lundell I, Paananen L, Wikberg JE, Männistö PT, Larhammar D. Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea-pig. Br J Pharmacol. 2002 Apr;135(8):2029-37. doi: 10.1038/sj.bjp.0704667. PMID: 11959807; PMCID: PMC1573328.
In vivo protocol:
1. Costa-e-Sousa RH, Souza LL, Calviño C, Cabanelas A, Almeida NA, Oliveira KJ, Pazos-Moura CC. Central NPY-Y5 receptors activation plays a major role in fasting-induced pituitary-thyroid axis suppression in adult rat. Regul Pept. 2011 Nov 10;171(1-3):43-7. doi: 10.1016/j.regpep.2011.07.001. Epub 2011 Jul 21. PMID: 21771616.
1: He H, Tran P, Gu H, Tedesco V, Zhang J, Lin W, Gatlik E, Klein K, Heimbach T. Midostaurin, a Novel Protein Kinase Inhibitor for the Treatment of Acute Myelogenous Leukemia: Insights from Human Absorption, Metabolism, and Excretion Studies of a BDDCS II Drug. Drug Metab Dispos. 2017 May;45(5):540-555. doi: 10.1124/dmd.116.072744. Epub 2017 Mar 7. PMID: 28270565.
2: Gu H, Dutreix C, Rebello S, Ouatas T, Wang L, Chun DY, Einolf HJ, He H. Simultaneous Physiologically Based Pharmacokinetic (PBPK) Modeling of Parent and Active Metabolites to Investigate Complex CYP3A4 Drug-Drug Interaction Potential: A Case Example of Midostaurin. Drug Metab Dispos. 2018 Feb;46(2):109-121. doi: 10.1124/dmd.117.078006. Epub 2017 Nov 8. PMID: 29117990.
3: Dutreix C, Munarini F, Lorenzo S, Roesel J, Wang Y. Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers. Cancer Chemother Pharmacol. 2013 Dec;72(6):1223-34. doi: 10.1007/s00280-013-2287-6. Epub 2013 Oct 2. PMID: 24085261; PMCID: PMC3834177.
4: Peter B, Winter GE, Blatt K, Bennett KL, Stefanzl G, Rix U, Eisenwort G, Hadzijusufovic E, Gridling M, Dutreix C, Hoermann G, Schwaab J, Radia D, Roesel J, Manley PW, Reiter A, Superti-Furga G, Valent P. Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth. Leukemia. 2016 Feb;30(2):464-72. doi: 10.1038/leu.2015.242. Epub 2015 Sep 9. PMID: 26349526; PMCID: PMC4896384.
5: Wang Y, Yin OQ, Graf P, Kisicki JC, Schran H. Dose- and time-dependent pharmacokinetics of midostaurin in patients with diabetes mellitus. J Clin Pharmacol. 2008 Jun;48(6):763-75. doi: 10.1177/0091270008318006. PMID: 18508951.
