Ansamitocin P-3 | CAS#66584-72-3 | microtubule inhibitor

MedKoo Cat#: 123124 | Name: Ansamitocin P-3

Description:

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

Ansamitocin P-3 (AP-3) is an active and potent anti-tumor maytansinoid which is usually produced by Actinosynnema spp. Ansamitocin P-3 has shown potent cytotoxicity against the human solid tumor cell lines A-549 and HT-29. Ansamitocin P-3 is useful in synthesizing the anticancer drugs mertansine and emtansine.

Chemical Structure

Ansamitocin P-3

CAS#66584-72-3 (AP-3)

Theoretical Analysis

MedKoo Cat#: 123124

Name: Ansamitocin P-3

CAS#: 66584-72-3 (AP-3)

Chemical Formula: C32H43ClN2O9

Exact Mass: 634.2657

Molecular Weight: 635.15

Elemental Analysis: C, 60.51; H, 6.82; Cl, 5.58; N, 4.41; O, 22.67

Price and Availability

Size	Price	Availability
5mg	USD 110.00	Ready to ship
10mg	USD 180.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,450.00	Ready to ship

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Related CAS #

66547-09-9 (AP-3') 66584-72-3 (AP-3)

Synonym

NSC292222; NSC 292222; NSC-292222; Ansamitocin P-3; Ansamitocin P3; Ansamitocin P 3; Maytansinol isobutyrate, Maytansinoid AP-3.

IUPAC/Chemical Name

[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 2-methylpropanoate

InChi Key

OPQNCARIZFLNLF-JBHFWYGFSA-N

InChi Code

InChI=1S/C32H43ClN2O9/c1-17(2)29(37)43-25-15-26(36)35(6)21-13-20(14-22(40-7)27(21)33)12-18(3)10-9-11-24(41-8)32(39)16-23(42-30(38)34-32)19(4)28-31(25,5)44-28/h9-11,13-14,17,19,23-25,28,39H,12,15-16H2,1-8H3,(H,34,38)/b11-9+,18-10+/t19-,23+,24-,25+,28+,31+,32+/m1/s1

SMILES Code

C[C@@H]1[C@@H]2C[C@]([C@@H](/C=C/C=C(/CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)C[C@@H]([C@]4([C@H]1O4)C)OC(=O)C(C)C)C)\C)OC)(NC(=O)O2)O

Appearance

White to off-white solidw powder

Purity

>90% (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, not in water

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB60822

QC Data

View QC data: current batch, Lot#CRB60822

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ansamitocin P-3 (Antibiotic C 15003P3) is a microtubule inhibitor.

In vitro activity:

Treatment of SP37A3 cells with ansamitocin-P3 induced significant production of proinflammatory cytokines interleukin(IL)-1β, IL-6, and IL-12 at doses greater than 100 nM (Figure 1B). In addition, exposure to ansamitocin-P3 induced the expression of the costimulatory molecules CD80, CD86, and CD40 (Figure 1C; Figure S1B). The dosing used for the MDAs favorably compares with the dosing used in clinics. Reference: Cell Rep. 2019 Sep 24; 28(13): 3367–3380.e8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876861/

In vivo activity:

Significantly more LN-resident DCs were FITC-Dx/CD86-positive in ansamitocin P3-treated mice (20 %) compared with vehicle control-treated mice (0.3 %; Fig. 3a, b). FITC-Dx-bearing DCs were not detected in non-tumor-draining LNs in either case, arguing for local, tumor-selective effects of ansamitocin P3 treatment (data not shown). Enhanced activation of antigen-specific T cells in the presence of ansamitocin P3 was confirmed in vivo: Transgenic CD8+ and CD4+ T cells specific for OVA isolated from OT-I to OT-II mice, respectively, were adoptively transferred into Ly5.1 congenic recipient mice, which were immunized with a weak agonist peptide derived from the original OVA peptide SIINFEKL for OT-I T cells and the natural OVA323–339 peptide for OT-II i cells together with ansamitocin P3, LPS, or vehicle (PBS). Both ansamitocin P3 and LPS effectively induced strong proliferation of OT-I and OT-II T cells after 3 days (Fig. 3c). Reference: Cancer Immunol Immunother. 2014 Sep;63(9):925-38. https://link.springer.com/article/10.1007%2Fs00262-014-1565-4

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	157.44
	Ethanol	55.0	86.59

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 635.15 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. Wang X, Wang R, Kang Q, Bai L. The Antitumor Agent Ansamitocin P-3 Binds to Cell Division Protein FtsZ in Actinosynnema pretiosum. Biomolecules. 2020 Apr 30;10(5):699. doi: 10.3390/biom10050699. PMID: 32365857; PMCID: PMC7277737. 2. Kashyap AS, Fernandez-Rodriguez L, Zhao Y, Monaco G, Trefny MP, Yoshida N, Martin K, Sharma A, Olieric N, Shah P, Stanczak M, Kirchhammer N, Park SM, Wieckowski S, Laubli H, Zagani R, Kasenda B, Steinmetz MO, Reinecker HC, Zippelius A. GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses. Cell Rep. 2019 Sep 24;28(13):3367-3380.e8. doi: 10.1016/j.celrep.2019.08.057. PMID: 31553907; PMCID: PMC6876861. 3. Martin K, Müller P, Schreiner J, Prince SS, Lardinois D, Heinzelmann-Schwarz VA, Thommen DS, Zippelius A. The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity. Cancer Immunol Immunother. 2014 Sep;63(9):925-38. doi: 10.1007/s00262-014-1565-4. Epub 2014 Jun 7. PMID: 24906866.

In vitro protocol:

In vivo protocol:

1. Martin K, Müller P, Schreiner J, Prince SS, Lardinois D, Heinzelmann-Schwarz VA, Thommen DS, Zippelius A. The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity. Cancer Immunol Immunother. 2014 Sep;63(9):925-38. doi: 10.1007/s00262-014-1565-4. Epub 2014 Jun 7. PMID: 24906866.

1: Wang X, Wei J, Xiao Y, Luan S, Ning X, Bai L. Efflux identification and engineering for ansamitocin P-3 production in Actinosynnema pretiosum. Appl Microbiol Biotechnol. 2021 Jan;105(2):695-706. doi: 10.1007/s00253-020-11044-6. Epub 2021 Jan 4. PMID: 33394151. 2: Zhu X, Hou K, Zheng P, Zhong W, Guo J, Zhao X, Hong T, Cai Z. Improvement of Biosynthetic Ansamitocin P-3 Production Based on Oxygen-Vector Screening and Metabonomics Analysis. Evid Based Complement Alternat Med. 2022 Jun 2;2022:3564185. doi: 10.1155/2022/3564185. PMID: 35692578; PMCID: PMC9184225. 3: Wang X, Wang R, Kang Q, Bai L. The Antitumor Agent Ansamitocin P-3 Binds to Cell Division Protein FtsZ in Actinosynnema pretiosum. Biomolecules. 2020 Apr 30;10(5):699. doi: 10.3390/biom10050699. PMID: 32365857; PMCID: PMC7277737. 4: Liu T, Yang L, Chen J, Hu F, Wei LJ, Hua Q. Metabolomic change and pathway profiling reveal enhanced ansamitocin P-3 production in Actinosynnema pretiosum with low organic nitrogen availability in culture medium. Appl Microbiol Biotechnol. 2020 Apr;104(8):3555-3568. doi: 10.1007/s00253-020-10463-9. Epub 2020 Feb 29. PMID: 32114676. 5: Izawa M, Wada Y, Kasahara F, Asai M, Kishi T. Hydroxylation of ansamitocin P-3. J Antibiot (Tokyo). 1981 Dec;34(12):1591-5. doi: 10.7164/antibiotics.34.1591. PMID: 7333973. 6: Du ZQ, Zhong JJ. Rational approach to improve ansamitocin P-3 production by integrating pathway engineering and substrate feeding in Actinosynnema pretiosum. Biotechnol Bioeng. 2018 Oct;115(10):2456-2466. doi: 10.1002/bit.26775. Epub 2018 Jul 20. PMID: 29940067. 7: Li T, Fan Y, Nambou K, Hu F, Imanaka T, Wei L, Hua Q. Improvement of ansamitocin P-3 production by Actinosynnema mirum with fructose as the sole carbon source. Appl Biochem Biotechnol. 2015 Mar;175(6):2845-56. doi: 10.1007/s12010-014-1445-6. Epub 2015 Jan 7. PMID: 25564203. 8: Jin Y, Tomeh MA, Zhang P, Su M, Zhao X, Cai Z. Microfluidic fabrication of photo-responsive Ansamitocin P-3 loaded liposomes for the treatment of breast cancer. Nanoscale. 2023 Feb 23;15(8):3780-3795. doi: 10.1039/d2nr06215a. PMID: 36723377. 9: Suwanborirux K, Chang CJ, Spjut RW, Cassady JM. Ansamitocin P-3, a maytansinoid, from Claopodium crispifolium and Anomodon attenuatus or associated actinomycetes. Experientia. 1990 Jan 15;46(1):117-20. doi: 10.1007/BF01955435. PMID: 2298279. 10: Segraves NL, Yazzie D, Deese AJ. An isolable acyclic hemiacetal of ansamitocin P-3. Magn Reson Chem. 2012 Mar;50(3):256-9. doi: 10.1002/mrc.2876. Epub 2012 Feb 28. PMID: 22374862. 11: Lin J, Bai L, Deng Z, Zhong JJ. Enhanced production of ansamitocin P-3 by addition of isobutanol in fermentation of Actinosynnema pretiosum. Bioresour Technol. 2011 Jan;102(2):1863-8. doi: 10.1016/j.biortech.2010.09.102. Epub 2010 Oct 25. PMID: 20980145. 12: Li J, Sun R, Ning X, Wang X, Wang Z. Genome-Scale Metabolic Model of Actinosynnema pretiosum ATCC 31280 and Its Application for Ansamitocin P-3 Production Improvement. Genes (Basel). 2018 Jul 20;9(7):364. doi: 10.3390/genes9070364. PMID: 30036981; PMCID: PMC6070911. 13: Fan Y, Gao Y, Zhou J, Wei L, Chen J, Hua Q. Process optimization with alternative carbon sources and modulation of secondary metabolism for enhanced ansamitocin P-3 production in Actinosynnema pretiosum. J Biotechnol. 2014 Dec 20;192 Pt A:1-10. doi: 10.1016/j.jbiotec.2014.10.020. PMID: 25456055. 14: Gao Y, Fan Y, Nambou K, Wei L, Liu Z, Imanaka T, Hua Q. Enhancement of ansamitocin P-3 production in Actinosynnema pretiosum by a synergistic effect of glycerol and glucose. J Ind Microbiol Biotechnol. 2014 Jan;41(1):143-52. doi: 10.1007/s10295-013-1374-3. Epub 2013 Oct 31. PMID: 24174216. 15: Du ZQ, Zhang Y, Qian ZG, Xiao H, Zhong JJ. Combination of traditional mutation and metabolic engineering to enhance ansamitocin P-3 production in Actinosynnema pretiosum. Biotechnol Bioeng. 2017 Dec;114(12):2794-2806. doi: 10.1002/bit.26396. Epub 2017 Aug 23. Erratum in: Biotechnol Bioeng. 2018 Oct;115(10):2668. PMID: 28782796. 16: Lin J, Zhong JJ. Proteomic studies on anti-tumor agent ansamitocin P-3 producer Actinosynnema pretiosum in response to ammonium and isobutanol. Bioprocess Biosyst Eng. 2017 Jul;40(7):1133-1139. doi: 10.1007/s00449-017-1763-5. Epub 2017 Apr 5. PMID: 28382459. 17: Yao Y, Cheng Z, Ye H, Xie Y, He J, Tang M, Shen T, Wang J, Zhou Y, Lu Z, Luo F, Chen L, Yu L, Yang JL, Peng A, Wei Y. Preparative isolation and purification of anti-tumor agent ansamitocin P-3 from fermentation broth of Actinosynnema pretiosum using high-performance counter-current chromatography. J Sep Sci. 2010 May;33(9):1331-7. doi: 10.1002/jssc.200900746. PMID: 20235129. 18: Jia Y, Zhong JJ. Enhanced production of ansamitocin P-3 by addition of Mg2+ in fermentation of Actinosynnema pretiosum. Bioresour Technol. 2011 Nov;102(21):10147-50. doi: 10.1016/j.biortech.2011.08.031. Epub 2011 Aug 22. PMID: 21907573. 19: Ning X, Wang X, Wu Y, Kang Q, Bai L. Identification and Engineering of Post- PKS Modification Bottlenecks for Ansamitocin P-3 Titer Improvement in Actinosynnema pretiosum subsp. pretiosum ATCC 31280. Biotechnol J. 2017 Nov;12(11). doi: 10.1002/biot.201700484. Epub 2017 Sep 25. PMID: 28881098. 20: Liu Z, Floss HG, Cassady JM, Chan KK. Metabolism studies of the anti-tumor agent maytansine and its analog ansamitocin P-3 using liquid chromatography/tandem mass spectrometry. J Mass Spectrom. 2005 Mar;40(3):389-99. doi: 10.1002/jms.800. PMID: 15674857.