Synonym
MY 5445; MY5445; MY-5445
IUPAC/Chemical Name
1-Phthalazinamine, N-(3-chlorophenyl)-4-phenyl-
InChi Key
CEHQLKSLMFIHBF-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H14ClN3/c21-15-9-6-10-16(13-15)22-20-18-12-5-4-11-17(18)19(23-24-20)14-7-2-1-3-8-14/h1-13H,(H,22,24)
SMILES Code
ClC1=CC(NC2=NN=C(C3=CC=CC=C3)C4=C2C=CC=C4)=CC=C1
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:
MY-5445 is a specific inhibitor of the cyclic GMP phosphodiesterase, phosphodiesterase type 5 (PDE5), with a Ki of 1.3 μM.
In vitro activity:
This study discovered that by inhibiting the drug transport function of ABCG2, MY-5445 potentiates drug-induced apoptosis in ABCG2-overexpressing multidrug-resistant cancer cells and resensitizes these cells to chemotherapeutic drugs. This study’s data of MY-5445 stimulating the ATPase activity of ABCG2 and molecular docking analysis of its binding to the substrate-binding pocket of ABCG2 provide additional insight into the manner in which MY-5445 interacts with ABCG2. Furthermore, this study found that ABCG2 does not confer resistance to MY-5445 in human cancer cells.
Reference: Am J Cancer Res. 2020 Jan 1;10(1):164-178. https://pubmed.ncbi.nlm.nih.gov/32064159/
In vivo activity:
The NO inhibitor, NG-monomethyl-L-arginine (50 micrograms/paw) and methylene blue (500 micrograms/paw) abolished the analgesic effect of dipyrone and myrcene. Dibutyryl cyclic adenosine monophosphate (DbcAMP) caused a dose-dependent hyperalgesia (20, 50 and 100 micrograms/paw). Only responses to low doses of DbcAMP were inhibited by the two analgesics. Pretreatment with MY5445 (50 micrograms/paw) resulted in potentiation of the effects of both analgesics.
Reference: Eur J Pharmacol. 1992 Jul 7;217(2-3):225-7. https://pubmed.ncbi.nlm.nih.gov/1330593/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
2.0 |
6.03 |
|
| DMSO |
26.0 |
78.36 |
|
| DMSO:PBS (pH 7.2) (1:2) |
0.3 |
0.90 |
|
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
331.80
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. Wu CP, Lusvarghi S, Tseng PJ, Hsiao SH, Huang YH, Hung TH, Ambudkar SV. MY-5445, a phosphodiesterase type 5 inhibitor, resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic anticancer drugs. Am J Cancer Res. 2020 Jan 1;10(1):164-178. PMID: 32064159; PMCID: PMC7017726.
2. Hagiwara M, Endo T, Kanayama T, Hidaka H. Effect of 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), a specific inhibitor of cyclic GMP phosphodiesterase, on human platelet aggregation. J Pharmacol Exp Ther. 1984 Feb;228(2):467-71. PMID: 6141286.
3. Xu HL, Wolde HM, Gavrilyuk V, Baughman VL, Pelligrino DA. cAMP modulates cGMP-mediated cerebral arteriolar relaxation in vivo. Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2501-9. doi: 10.1152/ajpheart.00319.2004. Epub 2004 Jul 22. PMID: 15271668.
4. Duarte ID, dos Santos IR, Lorenzetti BB, Ferreira SH. Analgesia by direct antagonism of nociceptor sensitization involves the arginine-nitric oxide-cGMP pathway. Eur J Pharmacol. 1992 Jul 7;217(2-3):225-7. doi: 10.1016/0014-2999(92)90881-4. PMID: 1330593.
In vitro protocol:
1. Wu CP, Lusvarghi S, Tseng PJ, Hsiao SH, Huang YH, Hung TH, Ambudkar SV. MY-5445, a phosphodiesterase type 5 inhibitor, resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic anticancer drugs. Am J Cancer Res. 2020 Jan 1;10(1):164-178. PMID: 32064159; PMCID: PMC7017726.
2. Hagiwara M, Endo T, Kanayama T, Hidaka H. Effect of 1-(3-chloroanilino)-4-phenylphthalazine (MY-5445), a specific inhibitor of cyclic GMP phosphodiesterase, on human platelet aggregation. J Pharmacol Exp Ther. 1984 Feb;228(2):467-71. PMID: 6141286.
In vivo protocol:
1. Xu HL, Wolde HM, Gavrilyuk V, Baughman VL, Pelligrino DA. cAMP modulates cGMP-mediated cerebral arteriolar relaxation in vivo. Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2501-9. doi: 10.1152/ajpheart.00319.2004. Epub 2004 Jul 22. PMID: 15271668.
2. Duarte ID, dos Santos IR, Lorenzetti BB, Ferreira SH. Analgesia by direct antagonism of nociceptor sensitization involves the arginine-nitric oxide-cGMP pathway. Eur J Pharmacol. 1992 Jul 7;217(2-3):225-7. doi: 10.1016/0014-2999(92)90881-4. PMID: 1330593.
1: Souness JE, Brazdil R, Diocee BK, Jordan R. Role of selective cyclic GMP phosphodiesterase inhibition in the myorelaxant actions of M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine. Br J Pharmacol. 1989 Nov;98(3):725-34. PubMed PMID: 2480168; PubMed Central PMCID: PMC1854783.
2: Zurbonsen K, Michel A, Vittet D, Bonnet PA, Chevillard C. Dissociation between phosphodiesterase inhibition and antiproliferative effects of phosphodiesterase inhibitors on the Dami cell line. Biochem Pharmacol. 1997 Apr 25;53(8):1141-7. PubMed PMID: 9175719.
3: Duarte ID, Ferreira SH. L-NAME causes antinociception by stimulation of the arginine-NO-cGMP pathway. Mediators Inflamm. 2000;9(1):25-30. PubMed PMID: 10877451; PubMed Central PMCID: PMC1781740.
4: Ito M, Nishikawa M, Fujioka M, Miyahara M, Isaka N, Shiku H, Nakano T. Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021. Cell Signal. 1996 Dec;8(8):575-81. PubMed PMID: 9115850.
5: Duarte ID, Ferreira SH. The molecular mechanism of central analgesia induced by morphine or carbachol and the L-arginine-nitric oxide-cGMP pathway. Eur J Pharmacol. 1992 Oct 6;221(1):171-4. PubMed PMID: 1333972.
6: Messina E, Lupi F, Barile L, Giacomello A. Cyclic nucleotides and neuroblastoma differentiation. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1551-4. PubMed PMID: 15571296.
7: Radomski MW, Palmer RM, Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1482-9. PubMed PMID: 2825688.
8: Ferreira SH, Duarte ID, Lorenzetti BB. The molecular mechanism of action of peripheral morphine analgesia: stimulation of the cGMP system via nitric oxide release. Eur J Pharmacol. 1991 Aug 16;201(1):121-2. PubMed PMID: 1665419.
9: Wu CC, Ko FN, Kuo SC, Lee FY, Teng CM. YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase. Br J Pharmacol. 1995 Oct;116(3):1973-8. PubMed PMID: 8640334; PubMed Central PMCID: PMC1908948.
10: Petritsch C, Woscholski R, Edelmann HM, Ballou LM. Activation of p70 S6 kinase and erk-encoded mitogen-activated protein kinases is resistant to high cyclic nucleotide levels in Swiss 3T3 fibroblasts. J Biol Chem. 1995 Nov 3;270(44):26619-25. PubMed PMID: 7592886.
11: Duarte ID, dos Santos IR, Lorenzetti BB, Ferreira SH. Analgesia by direct antagonism of nociceptor sensitization involves the arginine-nitric oxide-cGMP pathway. Eur J Pharmacol. 1992 Jul 7;217(2-3):225-7. PubMed PMID: 1330593.
12: Ferreira SH, Duarte ID, Lorenzetti BB. Molecular base of acetylcholine and morphine analgesia. Agents Actions Suppl. 1991;32:101-6. PubMed PMID: 1676874.
13: Akamatsu N, Inenaga K, Yamashita H. Inhibitory effects of natriuretic peptides on vasopressin neurons mediated through cGMP and cGMP-dependent protein kinase in vitro. J Neuroendocrinol. 1993 Oct;5(5):517-22. PubMed PMID: 8680419.
14: Lanza F, Beretz A, Stierlé A, Corre G, Cazenave JP. Cyclic nucleotide phosphodiesterase inhibitors prevent aggregation of human platelets by raising cyclic AMP and reducing cytoplasmic free calcium mobilization. Thromb Res. 1987 Mar 1;45(5):477-84. PubMed PMID: 3035738.
