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MedKoo Cat#: 530301 | Name: KNI-272

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Kynostatin-272, also known as KNI-272; NSC-651714; DRG-0219, is a HIV protease inhibitor potentially for the treatment of HIV infection. KNI-272 blocked the maturation of viral particles. Consequently, KNI-272 has at least two inhibition targets in the stages of the HIV-1 life cycle.

Chemical Structure

KNI-272
KNI-272
CAS#147318-81-8

Theoretical Analysis

MedKoo Cat#: 530301

Name: KNI-272

CAS#: 147318-81-8

Chemical Formula: C33H41N5O6S2

Exact Mass: 667.2498

Molecular Weight: 667.84

Elemental Analysis: C, 59.35; H, 6.19; N, 10.49; O, 14.37; S, 9.60

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.
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Related CAS #
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Synonym
Kynostatin-272; Kynostatin 272; Kynostatin272; KNI-272; NSC-651714; KNI272; NSC651714; DRG-0219; DRG 0219; DRG0219.
IUPAC/Chemical Name
(R)-N-(tert-butyl)-3-((2S,3S)-2-hydroxy-3-((R)-2-(2-(isoquinolin-5-yloxy)acetamido)-3-(methylthio)propanamido)-4-phenylbutanoyl)thiazolidine-4-carboxamide
InChi Key
NJBBLOIWMSYVCQ-VZTVMPNDSA-N
InChi Code
InChI=1S/C33H41N5O6S2/c1-33(2,3)37-31(42)26-19-46-20-38(26)32(43)29(40)24(15-21-9-6-5-7-10-21)36-30(41)25(18-45-4)35-28(39)17-44-27-12-8-11-22-16-34-14-13-23(22)27/h5-14,16,24-26,29,40H,15,17-20H2,1-4H3,(H,35,39)(H,36,41)(H,37,42)/t24-,25-,26-,29-/m0/s1
SMILES Code
O=C([C@H]1N(C([C@@H](O)[C@@H](NC([C@@H](NC(COC2=CC=CC3=C2C=CN=C3)=O)CSC)=O)CC4=CC=CC=C4)=O)CSC1)NC(C)(C)C
Appearance
Solid powder
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
>2 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

Preparing Stock Solutions

The following data is based on the product molecular weight 667.84 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.

Recalculate based on batch purity %
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
1: Adachi M, Ohhara T, Kurihara K, Tamada T, Honjo E, Okazaki N, Arai S, Shoyama Y, Kimura K, Matsumura H, Sugiyama S, Adachi H, Takano K, Mori Y, Hidaka K, Kimura T, Hayashi Y, Kiso Y, Kuroki R. Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolution X-ray and neutron crystallography. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4641-6. doi: 10.1073/pnas.0809400106. PubMed PMID: 19273847; PubMed Central PMCID: PMC2660780. 2: Matsumura H, Adachi M, Sugiyama S, Okada S, Yamakami M, Tamada T, Hidaka K, Hayashi Y, Kimura T, Kiso Y, Kitatani T, Maki S, Yoshikawa HY, Adachi H, Takano K, Murakami S, Inoue T, Kuroki R, Mori Y. Crystallization and preliminary neutron diffraction studies of HIV-1 protease cocrystallized with inhibitor KNI-272. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Nov 1;64(Pt 11):1003-6. doi: 10.1107/S1744309108029679. PubMed PMID: 18997326; PubMed Central PMCID: PMC2581681. 3: Doi M, Kimura T, Ishida T, Kiso Y. Rigid backbone moiety of KNI-272, a highly selective HIV protease inhibitor: methanol, acetone and dimethylsulfoxide solvated forms of 3-[3-benzyl-2-hydroxy-9-(isoquinolin-5-yloxy)-6-methylsulfanylmethyl-5,8-dioxo-4, 7-diazanonanoyl]-N-tert-butyl-1,3-thiazolidine-4-carboxamide. Acta Crystallogr B. 2004 Aug;60(Pt 4):433-7. PubMed PMID: 15258401. 4: Doi M, Ishida T, Katsuya Y, Sasaki M, Taniguchi T, Hasegawa H, Mimoto T, Kiso Y. KNI-272, a highly selective and potent peptidic HIV protease inhibitor. Acta Crystallogr C. 2001 Nov;57(Pt 11):1333-5. PubMed PMID: 11706266. 5: Churchill DR, Slade PM, Youle M, Gazzard BG, Weber JN. A phase I/II study of the safety and activity of a microsphere formulation of KNI-272 in patients with HIV-1 infection. J Antimicrob Chemother. 2001 Mar;47(3):353-5. PubMed PMID: 11222570. 6: Goto T, Nakano T, Kohno T, Morimatsu S, Morita C, Hong W, Kiso Y, Nakai M, Sano K. Targets of a protease inhibitor, KNI-272, in HIV-1-infected cells. J Med Virol. 2001 Mar;63(3):203-9. PubMed PMID: 11170058. 7: Velazquez-Campoy A, Luque I, Todd MJ, Milutinovich M, Kiso Y, Freire E. Thermodynamic dissection of the binding energetics of KNI-272, a potent HIV-1 protease inhibitor. Protein Sci. 2000 Sep;9(9):1801-9. PubMed PMID: 11045625; PubMed Central PMCID: PMC2144700. 8: Kiriyama A, Nishiura T, Yamaji H, Takada K. Physiologically based pharmacokinetics of KNI-272, a tripeptide HIV-1 protease inhibitor. Biopharm Drug Dispos. 1999 May;20(4):199-205. PubMed PMID: 10440795. 9: Humphrey RW, Wyvill KM, Nguyen BY, Shay LE, Kohler DR, Steinberg SM, Ueno T, Fukasawa T, Shintani M, Hayashi H, Mitsuya H, Yarchoan R. A phase I trial of the pharmacokinetics, toxicity, and activity of KNI-272, an inhibitor of HIV-1 protease, in patients with AIDS or symptomatic HIV infection. Antiviral Res. 1999 Feb;41(1):21-33. PubMed PMID: 10321576. 10: Kiriyama A, Nishiura T, Yamaji H, Takada K. Metabolic characterization of a tripeptide human immunodeficiency virus type 1 protease inhibitor, KNI-272, in rat liver microsomes. Antimicrob Agents Chemother. 1999 Mar;43(3):549-56. PubMed PMID: 10049266; PubMed Central PMCID: PMC89159. 11: Mueller BU, Anderson BD, Farley MQ, Murphy R, Zuckerman J, Jarosinski P, Godwin K, McCully CL, Mitsuya H, Pizzo PA, Balis FM. Pharmacokinetics of the protease inhibitor KNI-272 in plasma and cerebrospinal fluid in nonhuman primates after intravenous dosing and in human immunodeficiency virus-infected children after intravenous and oral dosing. Antimicrob Agents Chemother. 1998 Jul;42(7):1815-8. PubMed PMID: 9661027; PubMed Central PMCID: PMC105689. 12: Kiriyama A, Nishiura T, Ishino M, Yamamoto Y, Ogita I, Kiso Y, Takada K. Binding characteristics of KNI-272 to plasma proteins, a new potent tripeptide HIV protease inhibitor. Biopharm Drug Dispos. 1996 Dec;17(9):739-51. PubMed PMID: 8968527. 13: Ohno Y, Kiso Y, Kobayashi Y. Solution conformations of KNI-272, a tripeptide HIV protease inhibitor designed on the basis of substrate transition state: determined by NMR spectroscopy and simulated annealing calculations. Bioorg Med Chem. 1996 Sep;4(9):1565-72. PubMed PMID: 8894113. 14: Wang YX, Freedberg DI, Yamazaki T, Wingfield PT, Stahl SJ, Kaufman JD, Kiso Y, Torchia DA. Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272. Biochemistry. 1996 Aug 6;35(31):9945-50. Erratum in: Biochemistry 1997 Jan 7;36(1):280. PubMed PMID: 8756455. 15: Kiriyama A, Sugahara M, Yoshikawa Y, Kiso Y, Takada K. The bioavailability of oral dosage forms of a new HIV-1 protease inhibitor, KNI-272, in beagle dogs. Biopharm Drug Dispos. 1996 Mar;17(2):125-34. PubMed PMID: 8907719. 16: Chokekijchai S, Shirasaka T, Weinstein JN, Mitsuya H. In vitro anti-HIV-1 activity of HIV protease inhibitor KNI-272 in resting and activated cells: implications for its combined use with AZT or ddI. Antiviral Res. 1995 Sep;28(1):25-38. PubMed PMID: 8585758. 17: Baldwin ET, Bhat TN, Gulnik S, Liu B, Topol IA, Kiso Y, Mimoto T, Mitsuya H, Erickson JW. Structure of HIV-1 protease with KNI-272, a tight-binding transition-state analog containing allophenylnorstatine. Structure. 1995 Jun 15;3(6):581-90. PubMed PMID: 8590019. 18: Sugahara M, Kiriyama A, Hamada Y, Kiso Y, Takada K. Absorption of new HIV-1 protease inhibitor, KNI-272, after intraduodenal and intragastric administrations to rats: effect of solvent. Biopharm Drug Dispos. 1995 May;16(4):269-77. PubMed PMID: 7548776. 19: Baldwin ET, Bhat TN, Gulnik S, Liu B, Kiso Y, Mitsuya H, Erickson JW. Structure of HIV-1 protease with KNI-272: a transition state mimetic inhibitor containing allophenylnorstatine. Adv Exp Med Biol. 1995;362:445-9. PubMed PMID: 8540355. 20: Kiriyama A, Fujita K, Takemura S, Kuramoto H, Kiso Y, Takada K. Plasma pharmacokinetics and urinary and biliary excretion of a new potent tripeptide HIV-1 protease inhibitor, KNI-272, in rats after intravenous administration. Biopharm Drug Dispos. 1994 Oct;15(7):617-26. PubMed PMID: 7849237.