ICI 198583

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

MedKoo CAT#: 597163

CAS#: 112887-62-4

Description: ICI 198583 is an antifolate thymidylate synthase inhibitor.

Chemical Structure

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ICI 198583
CAS# 112887-62-4
Instruction

Theoretical Analysis

MedKoo Cat#: 597163
Name: ICI 198583
CAS#: 112887-62-4
Chemical Formula: C25H24N4O6
Exact Mass: 476.17
Molecular Weight: 476.480
Elemental Analysis: C, 63.02; H, 5.08; N, 11.76; O, 20.15

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

Request quote for custom synthesis

Synonym: ICI 198583; CB 3819; ICI-198583; ICI198583;

IUPAC/Chemical Name: (4-(((2-methyl-4-oxo-1,4-dihydroquinazolin-6-yl)methyl)(prop-2-yn-1-yl)amino)benzoyl)-L-glutamic acid

InChi Key: PMTUUSDTAKQWQJ-NRFANRHFSA-N

InChi Code: InChI=1S/C25H24N4O6/c1-3-12-29(14-16-4-9-20-19(13-16)24(33)27-15(2)26-20)18-7-5-17(6-8-18)23(32)28-21(25(34)35)10-11-22(30)31/h1,4-9,13,21H,10-12,14H2,2H3,(H,28,32)(H,30,31)(H,34,35)(H,26,27,33)/t21-/m0/s1

SMILES Code: O=C(O)CC[C@@H](C(O)=O)NC(C1=CC=C(N(CC2=CC3=C(NC(C)=NC3=O)C=C2)CC#C)C=C1)=O

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: >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: 2934.99.03.00

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 476.48 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
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Chen JH, Zhang N, Wang YQ, Wang JZ, Ji SX, Dang WJ, Li SM, Feng L. Estrogenic effects of flavonoid components in Xiaoyao powder. Genet Mol Res. 2016 Feb 11;15(1). doi: 10.4238/gmr.15017500. PubMed PMID: 26909969.

2: Pawełczak K, Makowski M, Kempny M, Dzik JM, Gołos B, Rode W, Rzeszotarska B. Sulfamide antifolates inhibiting thymidylate synthase: synthesis, enzyme inhibition and cytotoxicity. Acta Biochim Pol. 2002;49(2):407-20. PubMed PMID: 12362982.

3: Kusakiewicz-Dawid A, Bugaj M, Dzik JM, Gołos B, Wińska P, Pawełczak K, Rzeszotarska B, Rode W. Synthesis and biological activity of N(alpha)-[4-[N-[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]-N-propargylami no]phenylacetyl]-L-glutamic acid. Acta Biochim Pol. 2002;49(1):197-203. PubMed PMID: 12136941.

4: Skelton LA, Ormerod MG, Titley JC, Jackman AL. Cell cycle effects of CB30865, a lipophilic quinazoline-based analogue of the antifolate thymidylate synthase inhibitor ICI 198583 with an undefined mechanism of action. Cytometry. 1998 Sep 1;33(1):56-66. PubMed PMID: 9725559.

5: Bavetsias V, Jackman AL, Marriott JH, Kimbell R, Gibson W, Boyle FT, Bisset GM. Folate-based inhibitors of thymidylate synthase: synthesis and antitumor activity of gamma-linked sterically hindered dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583). J Med Chem. 1997 May 9;40(10):1495-510. PubMed PMID: 9154971.

6: Springer CJ, Bavetsias V, Jackman AL, Boyle FT, Marshall D, Pedley RB, Bisset GM. Prodrugs of thymidylate synthase inhibitors: potential for antibody directed enzyme prodrug therapy (ADEPT). Anticancer Drug Des. 1996 Dec;11(8):625-36. PubMed PMID: 9022750.

7: Bavetsias V, Jackman AL, Kimbell R, Gibson W, Boyle FT, Bisset GM. Quinazoline antifolate thymidylate synthase inhibitors: gamma-linked L-D, D-D, and D-L dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583). J Med Chem. 1996 Jan 5;39(1):73-85. PubMed PMID: 8568829.

8: Jackman AL, Kimbell R, Brown M, Brunton L, Bisset GM, Bavetsias V, Marsham P, Hughes LR, Boyle FT. Quinazoline-based thymidylate synthase inhibitors: relationship between structural modifications and polyglutamation. Anticancer Drug Des. 1995 Oct;10(7):573-89. PubMed PMID: 7495480.

9: Jackman AL, Kelland LR, Kimbell R, Brown M, Gibson W, Aherne GW, Hardcastle A, Boyle FT. Mechanisms of acquired resistance to the quinazoline thymidylate synthase inhibitor ZD1694 (Tomudex) in one mouse and three human cell lines. Br J Cancer. 1995 May;71(5):914-24. PubMed PMID: 7537518; PubMed Central PMCID: PMC2033796.

10: Marsham PR, Jackman AL, Barker AJ, Boyle FT, Pegg SJ, Wardleworth JM, Kimbell R, O'Connor BM, Calvert AH, Hughes LR. Quinazoline antifolate thymidylate synthase inhibitors: replacement of glutamic acid in the C2-methyl series. J Med Chem. 1995 Mar 17;38(6):994-1004. PubMed PMID: 7699716.

11: Bisset GM, Bavetsias V, Thornton TJ, Pawelczak K, Calvert AH, Hughes LR, Jackman AL. The synthesis and thymidylate synthase inhibitory activity of L-gamma-L-linked dipeptide and L-gamma-amide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583). J Med Chem. 1994 Sep 30;37(20):3294-302. PubMed PMID: 7932557.

12: Jansen M, Dykstra M, Lee JI, Stables J, Topley P, Knick VC, Mullin RJ, Duch DS, Smith GK. Effect of purine synthesis inhibition on WiDr spheroids in vitro or on WiDr or colon 38 tumors in vivo. Complete growth inhibition but not regression. Biochem Pharmacol. 1994 Mar 15;47(6):1067-78. PubMed PMID: 8147906.

13: Jodrell DI, Gibson W, Bisset GM, Boyle FT, Judson IR, Jackman AL. The in vivo metabolic stability of dipeptide analogues of the quinazoline antifolate, ICI 198583, in mice. Biochem Pharmacol. 1993 Dec 14;46(12):2229-34. PubMed PMID: 8274156.

14: Kimbell R, Jackman AL, Boyle FT, Hardcastle A, Aherne W. The duration of the inhibition of thymidylate synthase in intact L1210 cells exposed to two different classes of quinazoline analogues. Adv Exp Med Biol. 1993;338:597-600. PubMed PMID: 8304189.

15: Bavetsias V, Jackman AL, Thornton TJ, Pawelczak K, Boyle FT, Bisset GM. Quinazoline antifolates inhibiting thymidylate synthase: synthesis of gamma-linked peptide and amide analogues of 2-desamino-2-methyl-N10-propargyl- 5,8-dideazafolic acid (ICI 198583). Adv Exp Med Biol. 1993;338:593-6. PubMed PMID: 8304188.

16: Boyle FT, Matusiak ZS, Hughes LR, Slater AM, Stephens TC, Smith MN, Brown M, Kimbell R, Jackman AL. Substituted-2-desamino-2-methyl-quinazolinones. A series of novel antitumour agents. Adv Exp Med Biol. 1993;338:585-8. PubMed PMID: 8304185.

17: Jackman AL, Bisset GM, Jodrell DI, Gibson W, Kimbell R, Bavetsias V, Calvert AH, Harrap KR, Stephens TC, Smith MN, et al. Gamma-linked dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8- dideazafolate as antitumour agents. Adv Exp Med Biol. 1993;338:579-84. PubMed PMID: 8304184.

18: Jackman AL, Gibson W, Brown M, Kimbell R, Boyle FT. The role of the reduced-folate carrier and metabolism to intracellular polyglutamates for the activity of ICI D1694. Adv Exp Med Biol. 1993;339:265-76. Review. PubMed PMID: 7513935.

19: van der Laan BF, Jansen G, Kathmann GA, Westerhof GR, Schornagel JH, Hordijk GJ. In vitro activity of novel antifolates against human squamous carcinoma cell lines of the head and neck with inherent resistance to methotrexate. Int J Cancer. 1992 Jul 30;51(6):909-14. PubMed PMID: 1639538.

20: Kwok JB, Tattersall MH. DNA fragmentation, dATP pool elevation and potentiation of antifolate cytotoxicity in L1210 cells by hypoxanthine. Br J Cancer. 1992 Apr;65(4):503-8. PubMed PMID: 1562458; PubMed Central PMCID: PMC1977543.