Candicidin
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MedKoo CAT#: 598739

CAS#: 1403-17-4

Description: Candicidin is a mixture of antifungal heptaene macrolides from Streptomyces griseus or Actinomyces levoris used topically in candidiasis. The antibiotic complex is composed of candicidins A, B, C, and D, of which D is the major component.


Chemical Structure

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Candicidin
CAS# 1403-17-4

Theoretical Analysis

MedKoo Cat#: 598739
Name: Candicidin
CAS#: 1403-17-4
Chemical Formula: C59H84N2O18
Exact Mass: 1108.5719
Molecular Weight: 1109.31
Elemental Analysis: C, 63.88; H, 7.63; N, 2.53; O, 25.96

Price and Availability

Size Price Availability Quantity
1.0mg USD 455.0 2 Weeks
5.0mg USD 1415.0 2 Weeks
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Synonym: Candicidin; Candizidin; Levorinum; NSC 94219; NSC-94219; NSC94219;

IUPAC/Chemical Name: (23E,25E,27E,29E,31E,33E,35E)-22-(((3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-38-(7-(4-aminophenyl)-5-hydroxy-4-methyl-7-oxoheptan-2-yl)-10,12,14,18,20-pentahydroxy-37-methyl-2,4,8,16-tetraoxooxacyclooctatriaconta-23,25,27,29,31,33,35-heptaene-19-carboxylic acid

InChi Key: OPGSFDUODIJJGF-JBUZINEHSA-N

InChi Code: InChI=1S/C59H84N2O18/c1-35-18-15-13-11-9-7-5-6-8-10-12-14-16-21-47(78-59-56(74)54(61)55(73)38(4)77-59)33-51(71)53(58(75)76)50(70)31-46(67)30-45(66)29-44(65)28-43(64)27-41(62)19-17-20-42(63)32-52(72)79-57(35)37(3)26-36(2)48(68)34-49(69)39-22-24-40(60)25-23-39/h5-16,18,21-25,35-38,43-45,47-48,50-51,53-57,59,64-66,68,70-71,73-74H,17,19-20,26-34,60-61H2,1-4H3,(H,75,76)/b6-5+,9-7+,10-8+,13-11+,14-12+,18-15+,21-16+/t35?,36?,37?,38-,43?,44?,45?,47?,48?,50?,51?,53?,54+,55-,56+,57?,59?/m1/s1

SMILES Code: CC(C(CC(c1ccc(N)cc1)=O)O)CC(C2OC(CC(CCCC(CC(CC(CC(CC(CC(C(C(O)=O)C(CC(/C=C/C=C/C=C/C=C/C=C/C=C/C=C/C2C)OC3O[C@@H]([C@H]([C@@H]([C@@H]3O)N)O)C)O)O)=O)O)O)O)=O)=O)=O)C

Appearance: Solid powder

Purity: >95% (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

Product Data:

Biological target: Canertinib (CI-1033, PD183805) is a pan-ErbB inhibitor for EGFR and ErbB2 with IC50 of 1.5 nM and 9.0 nM, no activity to PDGFR, FGFR, InsR, PKC, or CDK1/2/4.
In vitro activity: Canertinib treatment of RaH3 and RaH5 with increasing concentrations (0–10 μM) for 72 h decreased the number of living cells in a dose-dependent manner (Fig. 1). Half-maximum growth inhibitory concentration (IC50), i.e. the dose required to inhibit serum stimulated growth by 50%, was estimated to 0.78 ± 0.08 μM in RaH3 and 0.80 ± 0.02 μM in RaH5. 5 μM canertinib completely inhibited growth (P < 0.01) and concentrations >5 μM induced dose-dependent cell death in both cell lines. Canertinib treatment of RaH3 and RaH5 cells with 1 μM for 24 h accumulated cells in the G1-phase of the cell cycle with a concomitant decrease in the S and G2/M cell cycle phase (Fig. 1C–F, Supplementary Table S1). Treatment of RaH3 and RaH5 cells with 10 μM of canertinib for up to 20 h decreased the number of cells in all cell cycle phases, also a time-dependent apoptotic sub-fraction of G1 cells appeared (Supplementary Fig. S1). Canertinib-induced apoptosis was confirmed by the Annexin V method, a time-dependent increase in apoptotic RaH3 and RaH5 cells occurred within 72 h of drug-exposure with 10 μM (Fig. 2C and D). Maximum apoptosis was achieved in RaH3 cells within 72 h (79%, P < 0.01) and in RaH5 cells within 48 h (76%, P < 0.001) of treatment (Fig. 2C and D). RaH3 and RaH5 cells treated with concentrations ⩾7.5 μM of canertinib for 48 h clearly induced apoptosis and with 10 μM apoptosis occurred in 56% (P < 0.05) and 76% (P < 0.001) of RaH3 and RaH5 cells, respectively (Fig. 2E and F). ErbB1 and ErbB3 phosphorylation was abolished within 30 min of 1 μM canertinib treatment of RaH3 and RaH5 and remained undetectable during the 6 h observation period as determined by Western blot (Fig. 3A). Canertinib treatment of RaH3 and RaH5 with 1 μM reduced Akt and Erk1/2 phosphorylation already within 30 min of incubation in both cell lines (Fig. 3B). Reference: Biochem Biophys Res Commun. 2011 Oct 28;414(3):563-8. https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(11)01733-5
In vivo activity: The growth of human malignant melanoma xenografts, RaH3 and RaH5, in nude mice was significantly inhibited by i.p. injections of 40 mg/kg/day canertinib (Fig. 4). The anti-proliferative effect on melanoma xenografts was visible already within 4 days of treatment and further increased throughout the treatment period as observed through the differences in tumor volumes, reaching statistical significance within 18 days of treatment (RaH3 P = 0.021 and RaH5 P = 0.014) (Fig. 4A and B). The growth inhibition of canertinib on RaH3 and RaH5 xenografts was also reflected by a significant decrease in tumor weights as compared to untreated tumors (Fig. 4C). The detectable side effects were mild including less than 8% weight loss in the treated mice compared to untreated animals, with no signs of skin rash, diarrhea or any other side effect, all animals seemed to thrive despite treatment. However, one RaH5 xenograft-bearing mouse died in the treatment group at day 5 without showing any signs of illness. Reference: Biochem Biophys Res Commun. 2011 Oct 28;414(3):563-8. https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(11)01733-5

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 4.9 10.08
Ethanol 12.5 25.72

Preparing Stock Solutions

The following data is based on the product molecular weight 1109.31 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
In vitro protocol: 1. Djerf Severinsson EA, Trinks C, Gréen H, Abdiu A, Hallbeck AL, Stål O, Walz TM. The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma in vitro and displays anti-tumor activity in vivo. Biochem Biophys Res Commun. 2011 Oct 28;414(3):563-8. doi: 10.1016/j.bbrc.2011.09.118. Epub 2011 Oct 1. PMID: 21982771. 2. Ako E, Yamashita Y, Ohira M, Yamazaki M, Hori T, Kubo N, Sawada T, Hirakawa K. The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo. Oncol Rep. 2007 Apr;17(4):887-93. doi: 10.3892/or.17.4.887. PMID: 17342332.
In vivo protocol: 1. Djerf Severinsson EA, Trinks C, Gréen H, Abdiu A, Hallbeck AL, Stål O, Walz TM. The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma in vitro and displays anti-tumor activity in vivo. Biochem Biophys Res Commun. 2011 Oct 28;414(3):563-8. doi: 10.1016/j.bbrc.2011.09.118. Epub 2011 Oct 1. PMID: 21982771. 2. Ako E, Yamashita Y, Ohira M, Yamazaki M, Hori T, Kubo N, Sawada T, Hirakawa K. The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo. Oncol Rep. 2007 Apr;17(4):887-93. doi: 10.3892/or.17.4.887. PMID: 17342332.

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1: Szwarc K, Szczeblewski P, Sowiński P, Borowski E, Pawlak J. The stereostructure of candicidin D. J Antibiot (Tokyo). 2015 Aug;68(8):504-10. doi: 10.1038/ja.2015.17. Epub 2015 Feb 25. PubMed PMID: 25712395.

2: Zhang P, Zhao Z, Li H, Chen XL, Deng Z, Bai L, Pang X. Production of the antibiotic FR-008/candicidin in Streptomyces sp. FR-008 is co-regulated by two regulators, FscRI and FscRIV, from different transcription factor families. Microbiology. 2015 Mar;161(Pt 3):539-52. doi: 10.1099/mic.0.000033. Epub 2015 Jan 9. PubMed PMID: 25575546.

3: Lei X, Kong L, Zhang C, Liu Q, Yao F, Zhang W, Deng Z, You D. In vivo investigation of the substrate recognition capability and activity affecting amino acid residues of glycosyltransferase FscMI in the biosynthesis of candicidin. Mol Biosyst. 2013 Mar;9(3):422-30. doi: 10.1039/c2mb25464f. Epub 2013 Jan 17. PubMed PMID: 23324745.

4: Lei X, Kong L, Zhang C, You D, Deng Z. [Function of transporter genes fscTI and fscTII in the biosynthetic cluster of candicidin/FR-008]. Wei Sheng Wu Xue Bao. 2012 Dec 4;52(12):1458-66. Chinese. PubMed PMID: 23457795.

5: McLean TC, Hoskisson PA, Seipke RF. Coordinate Regulation of Antimycin and Candicidin Biosynthesis. mSphere. 2016 Dec 7;1(6). pii: e00305-16. eCollection 2016 Nov-Dec. PubMed PMID: 27981234; PubMed Central PMCID: PMC5143413.

6: Martín JF, Aparicio JF. Enzymology of the polyenes pimaricin and candicidin biosynthesis. Methods Enzymol. 2009;459:215-42. doi: 10.1016/S0076-6879(09)04610-2. PubMed PMID: 19362642.

7: Gil JA, Campelo-Diez AB. Candicidin biosynthesis in Streptomyces griseus. Appl Microbiol Biotechnol. 2003 Feb;60(6):633-42. Epub 2002 Dec 18. Review. PubMed PMID: 12664141.

8: Jørgensen H, Fjaervik E, Hakvåg S, Bruheim P, Bredholt H, Klinkenberg G, Ellingsen TE, Zotchev SB. Candicidin biosynthesis gene cluster is widely distributed among Streptomyces spp. isolated from the sediments and the neuston layer of the Trondheim fjord, Norway. Appl Environ Microbiol. 2009 May;75(10):3296-303. doi: 10.1128/AEM.02730-08. Epub 2009 Mar 13. PubMed PMID: 19286787; PubMed Central PMCID: PMC2681660.

9: Martin JF, Mcdaniel LE. Specific inhibition of candicidin biosynthesis by the lipogenic inhibitor cerulenin. Biochim Biophys Acta. 1975 Dec 5;411(2):186-94. PubMed PMID: 811262.

10: Liu DM, McDaniel LE, Schaffner CP. Factors affecting the production of candicidin. Antimicrob Agents Chemother. 1975 Feb;7(2):196-202. PubMed PMID: 806261; PubMed Central PMCID: PMC429103.

11: Chen S, Mao X, Shen Y, Zhou Y, Li J, Wang L, Tao X, Yang L, Wang Y, Zhou X, Deng Z, Wei D. Tailoring the P450 monooxygenase gene for FR-008/candicidin biosynthesis. Appl Environ Microbiol. 2009 Mar;75(6):1778-81. doi: 10.1128/AEM.00859-08. Epub 2009 Jan 9. PubMed PMID: 19139241; PubMed Central PMCID: PMC2655452.

12: Haeder S, Wirth R, Herz H, Spiteller D. Candicidin-producing Streptomyces support leaf-cutting ants to protect their fungus garden against the pathogenic fungus Escovopsis. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4742-6. doi: 10.1073/pnas.0812082106. Epub 2009 Mar 6. PubMed PMID: 19270078; PubMed Central PMCID: PMC2660719.

13: Asturias JA, Martín JF, Liras P. Biosynthesis and phosphate control of candicidin by Streptomyces acrimycini JI2236: effect of amplification of the pabAB gene. J Ind Microbiol. 1994 May;13(3):183-9. PubMed PMID: 7764844.

14: Singhal AK, Mosbach EH, Schaffner CP. Effect of candicidin on cholesterol and bile acid metabolism in the rat. Lipids. 1981 Jun;16(6):423-6. PubMed PMID: 7266266.

15: Szwarc K, Szczeblewski P, Sowiński P, Borowski E, Pawlak J. The structure, including stereochemistry, of levorin A1. Magn Reson Chem. 2015 Jun;53(6):479-84. doi: 10.1002/mrc.4229. Epub 2015 Mar 13. PubMed PMID: 25773336.

16: Seipke RF, Barke J, Brearley C, Hill L, Yu DW, Goss RJ, Hutchings MI. A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus. PLoS One. 2011;6(8):e22028. doi: 10.1371/journal.pone.0022028. Epub 2011 Aug 3. PubMed PMID: 21857911; PubMed Central PMCID: PMC3153929.

17: Martín JF, Naharro G, Liras P, Villanueva JR. Isolation of mutants deregulated in phosphate control of candicidin biosynthesis. J Antibiot (Tokyo). 1979 Jun;32(6):600-6. PubMed PMID: 112091.

18: Kivinen S, Tarkkila T, Laakso L, Laakso K. Short-term topical treatment of vulvovaginal candidiasis with the combination of 5-fluorocytosine and candicidin. Curr Med Res Opin. 1979;6(2):88-92. PubMed PMID: 467093.

19: Zhou Y, Li J, Zhu J, Chen S, Bai L, Zhou X, Wu H, Deng Z. Incomplete beta-ketone processing as a mechanism for polyene structural variation in the FR-008/candicidin complex. Chem Biol. 2008 Jun;15(6):629-38. doi: 10.1016/j.chembiol.2008.05.007. PubMed PMID: 18559273.

20: Madsen PO, Dørflinger T, Frimodt-Møller PC, Jensen KM. Candicidin in treatment of benign prostatic hypertrophy. J Urol. 1984 Dec;132(6):1235-8. PubMed PMID: 6209428.