Phortress | CAS#328087-38-3 | CAS#741241-36-1 | Apoptosis Stimulant

MedKoo Cat#: 527705 | Name: Phortress

Description:

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

Phortress, also known as NSC-710305 and 5F-DF-203-L-lysinamide, is an apoptosis stimulant potentially for the treatment of solid tumours. Phortress had no effect on HUVEC and MRCV cell proliferation and survival. Unlike paclitaxel and fumagillin, Phortress did not inhibit endothelial tube differentiation. Phortress therefore exhibits no in vitro anti-angiogenic activity. As expected, Phortress was cytotoxic to MCF7 breast cancer cells, but unexpectedly, Phortress was also potent against colorectal cancer cells in clonogenic survival and cell growth (growth curves but not MTS assay) end-points.

Chemical Structure

Phortress

CAS#328087-38-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 527705

Name: Phortress

CAS#: 328087-38-3 (HCl)

Chemical Formula: C20H25Cl2FN4OS

Exact Mass: 0.0000

Molecular Weight: 459.41

Elemental Analysis: C, 52.29; H, 5.49; Cl, 15.43; F, 4.14; N, 12.20; O, 3.48; S, 6.98

Price and Availability

Size	Price	Availability
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 1,950.00	2 Weeks
500mg	USD 2,950.00	2 Weeks
1g	USD 4,250.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

328087-38-3 (HCl) 741241-36-1 (free)

Synonym

Phortress; NSC-710305; NSC-710305; NSC-710305; 5F-DF-203-L-lysinamide; 5FDF 203Llysinamide

IUPAC/Chemical Name

(S)-2,6-diamino-N-(4-(5-fluorobenzo[d]thiazol-2-yl)-2-methylphenyl)hexanamide dihydrochloride

InChi Key

QZSMNTOCJVVFEU-CKUXDGONSA-N

InChi Code

InChI=1S/C20H23FN4OS.2ClH/c1-12-10-13(20-25-17-11-14(21)6-8-18(17)27-20)5-7-16(12)24-19(26)15(23)4-2-3-9-22;;/h5-8,10-11,15H,2-4,9,22-23H2,1H3,(H,24,26);2*1H/t15-;;/m0../s1

SMILES Code

NCCCC[C@H](N)C(NC1=CC=C(C2=NC(C=C(F)C=C3)=C3S2)C=C1C)=O.Cl.Cl

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Phortress is a high affinity AhR ligand that elicits antitumor activity by inducing transcription of CYP1A1.

In vitro activity:

An ex vivo precision-cut lung slice (PCLS) model was used to search for concentration dependent effects of NSC 710305 (10, 25, 50, and 100 µM) on cytokine content, protein content, and immuno/histological endpoints. Preparation and culture of PCLS caused an initial spike in proinflammatory cytokine expression and therefore treatment with NSC 710305 was delayed until 48 h after initiating the slice cultures to avoid confounding the response to slicing with any drug response. PCLSs were evaluated after 24, 48, and 72 h exposures to NSC 710305. NSC 710305 caused a concentration-dependent cytokine response, and only the toxicity caused by a 72-h exposure to 25 µM reversed during the 24-h recovery period. Immuno/histological examination and quantitation of tissue protein levels indicated that tissue destruction, ED-1 (activated macrophage) staining, and protein levels were associated with the levels of proinflammatory cytokines in the tissue. In conclusion, the concentration- and time-dependent inflammatory response of PCLS to NSC 710305 preceded relevant tissue damage by a few days. Reference: Toxicol Sci. 2013 Feb;131(2):470-9. https://pubmed.ncbi.nlm.nih.gov/23143926/

In vivo activity:

Following treatment of xenograft-bearing mice and mice possessing hollow fiber implants containing MCF-7 or MDA-MB-435 cells with Phortress (20 mg/kg, i.p., 24 hours), tumor cells and xenografts were recovered for analyses by SCGE. Dose- and time-dependent DNA single and double strand breaks occurred exclusively in sensitive cells following treatment with 5F 203 in vitro (10 nmol/L-10 micromol/L; 24-72 hours). In vivo, Phortress-sensitive and Phortress-resistant tumor cells were distinct; moreover, DNA damage in xenografts, following treatment of mice with Phortress, could be determined. Reference: Mol Cancer Ther. 2004 Dec;3(12):1565-75. https://pubmed.ncbi.nlm.nih.gov/15634650/

	Solvent	mg/mL	mM
Solubility
	DMF	10.0	21.77
	DMSO	30.0	65.30
	PBS (pH 7.2)	10.0	21.77

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 459.41 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. Behrsing HP, Furniss MJ, Davis M, Tomaszewski JE, Parchment RE. In vitro exposure of precision-cut lung slices to 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole lysylamide dihydrochloride (NSC 710305, Phortress) increases inflammatory cytokine content and tissue damage. Toxicol Sci. 2013 Feb;131(2):470-9. doi: 10.1093/toxsci/kfs319. Epub 2012 Nov 9. PMID: 23143926; PMCID: PMC3551430. 2. Mukherjee A, Martin SG. In vitro cytotoxicity of Phortress against colorectal cancer. Int J Oncol. 2006 Nov;29(5):1287-94. PMID: 17016663. 3. Martinez JM, Sali T, Okazaki R, Anna C, Hollingshead M, Hose C, Monks A, Walker NJ, Baek SJ, Eling TE. Drug-induced expression of nonsteroidal anti-inflammatory drug-activated gene/macrophage inhibitory cytokine-1/prostate-derived factor, a putative tumor suppressor, inhibits tumor growth. J Pharmacol Exp Ther. 2006 Aug;318(2):899-906. doi: 10.1124/jpet.105.100081. Epub 2006 May 19. PMID: 16714403. 4. Leong CO, Suggitt M, Swaine DJ, Bibby MC, Stevens MF, Bradshaw TD. In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles. Mol Cancer Ther. 2004 Dec;3(12):1565-75. PMID: 15634650.

In vitro protocol:

In vivo protocol:

1. Martinez JM, Sali T, Okazaki R, Anna C, Hollingshead M, Hose C, Monks A, Walker NJ, Baek SJ, Eling TE. Drug-induced expression of nonsteroidal anti-inflammatory drug-activated gene/macrophage inhibitory cytokine-1/prostate-derived factor, a putative tumor suppressor, inhibits tumor growth. J Pharmacol Exp Ther. 2006 Aug;318(2):899-906. doi: 10.1124/jpet.105.100081. Epub 2006 May 19. PMID: 16714403. 2. Leong CO, Suggitt M, Swaine DJ, Bibby MC, Stevens MF, Bradshaw TD. In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles. Mol Cancer Ther. 2004 Dec;3(12):1565-75. PMID: 15634650.

1: Haid S, Matthaei A, Winkler M, Sake SM, Gunesch AP, Milke V, Köhler NM, Rückert J, Vieyres G, Kühl D, Nguyen T-T, Göhl M, Lasswitz L, Zapatero-Belinchón FJ, Brogden G, Gerold G, Wiegmann B, Bilitewski U, Brown RJP, Brönstrup M, Schulz TF, Pietschmann T. Repurposing screen identifies novel candidates for broad-spectrum coronavirus antivirals and druggable host targets. Antimicrob Agents Chemother. 2024 Mar 6;68(3):e0121023. doi: 10.1128/aac.01210-23. Epub 2024 Feb 6. PMID: 38319076; PMCID: PMC10916382. 2: Kuzu B, Hepokur C, Turkmenoglu B, Burmaoglu S, Algul O. Design, synthesis and in vitro antiproliferation activity of some 2-aryl and -heteroaryl benzoxazole derivatives. Future Med Chem. 2022 Jul;14(14):1027-1048. doi: 10.4155/fmc-2022-0076. Epub 2022 Jun 15. PMID: 35703122. 3: Sneha S, Baker SC, Green A, Storr S, Aiyappa R, Martin S, Pors K. Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies. Biomedicines. 2021 Mar 12;9(3):290. doi: 10.3390/biomedicines9030290. PMID: 33809117; PMCID: PMC7998590. 4: Osmaniye D, Korkut Çelikateş B, Sağlık BN, Levent S, Acar Çevik U, Kaya Çavuşoğlu B, Ilgın S, Özkay Y, Kaplancıklı ZA. Synthesis of some new benzoxazole derivatives and investigation of their anticancer activities. Eur J Med Chem. 2021 Jan 15;210:112979. doi: 10.1016/j.ejmech.2020.112979. Epub 2020 Oct 31. PMID: 33183865. 5: Itkin B, Breen A, Turyanska L, Sandes EO, Bradshaw TD, Loaiza-Perez AI. New Treatments in Renal Cancer: The AhR Ligands. Int J Mol Sci. 2020 May 18;21(10):3551. doi: 10.3390/ijms21103551. PMID: 32443455; PMCID: PMC7279047. 6: Breen AF, Scurr D, Cassioli ML, Wells G, Thomas NR, Zhang J, Turyanska L, Bradshaw TD. Protein Encapsulation of Experimental Anticancer Agents 5F 203 and Phortress: Towards Precision Drug Delivery. Int J Nanomedicine. 2019 Dec 5;14:9525-9534. doi: 10.2147/IJN.S226293. PMID: 31824148; PMCID: PMC6901036. 7: Cui J, Li S. Inhibitors and prodrugs targeting CYP1: a novel approach in cancer prevention and therapy. Curr Med Chem. 2014;21(5):519-52. doi: 10.2174/09298673113206660277. PMID: 24083611. 8: Zhang Y, Chakraborty M, Cerda-Smith CG, Bratton RN, Maurer NE, Senser EM, Novak M. Chemistry of ring-substituted 4-(benzothiazol-2-yl)phenylnitrenium ions from antitumor 2-(4-aminophenyl)benzothiazoles. J Org Chem. 2013 Jul 19;78(14):6992-7000. doi: 10.1021/jo400826f. Epub 2013 Jul 1. PMID: 23786256; PMCID: PMC3740366. 9: Behrsing HP, Furniss MJ, Davis M, Tomaszewski JE, Parchment RE. In vitro exposure of precision-cut lung slices to 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole lysylamide dihydrochloride (NSC 710305, Phortress) increases inflammatory cytokine content and tissue damage. Toxicol Sci. 2013 Feb;131(2):470-9. doi: 10.1093/toxsci/kfs319. Epub 2012 Nov 9. PMID: 23143926; PMCID: PMC3551430. 10: Bradshaw TD, Wren JE, Bruce M, Barrett DA, Leong CO, Gaskell M, Wright EK, Farmer PB, Henderson CJ, Wolf R, Stevens MF. Preclinical toxicokinetic evaluation of phortress [2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole lysylamide dihydrochloride] in two rodent species. Pharmacology. 2009;83(2):99-109. doi: 10.1159/000183846. Epub 2008 Dec 17. PMID: 19088497. 11: Mukherjee A, Martin SG. In vitro cytotoxicity of Phortress against colorectal cancer. Int J Oncol. 2006 Nov;29(5):1287-94. PMID: 17016663. 12: Martinez JM, Sali T, Okazaki R, Anna C, Hollingshead M, Hose C, Monks A, Walker NJ, Baek SJ, Eling TE. Drug-induced expression of nonsteroidal anti- inflammatory drug-activated gene/macrophage inhibitory cytokine-1/prostate- derived factor, a putative tumor suppressor, inhibits tumor growth. J Pharmacol Exp Ther. 2006 Aug;318(2):899-906. doi: 10.1124/jpet.105.100081. Epub 2006 May 19. PMID: 16714403. 13: Brantley E, Antony S, Kohlhagen G, Meng L, Agama K, Stinson SF, Sausville EA, Pommier Y. Anti-tumor drug candidate 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole induces single-strand breaks and DNA-protein cross-links in sensitive MCF-7 breast cancer cells. Cancer Chemother Pharmacol. 2006 Jul;58(1):62-72. doi: 10.1007/s00280-005-0127-z. Epub 2005 Dec 6. PMID: 16331501. 14: Leong CO, Suggitt M, Swaine DJ, Bibby MC, Stevens MF, Bradshaw TD. In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles. Mol Cancer Ther. 2004 Dec;3(12):1565-75. PMID: 15634650. 15: Fichtner I, Monks A, Hose C, Stevens MF, Bradshaw TD. The experimental antitumor agents Phortress and doxorubicin are equiactive against human-derived breast carcinoma xenograft models. Breast Cancer Res Treat. 2004 Sep;87(1):97-107. doi: 10.1023/B:BREA.0000041586.64371.88. PMID: 15377855. 16: Rooney PH, Telfer C, McFadyen MC, Melvin WT, Murray GI. The role of cytochrome P450 in cytotoxic bioactivation: future therapeutic directions. Curr Cancer Drug Targets. 2004 May;4(3):257-65. doi: 10.2174/1568009043333014. PMID: 15134533. 17: Bradshaw TD, Westwell AD. The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate. Curr Med Chem. 2004 Apr;11(8):1009-21. doi: 10.2174/0929867043455530. PMID: 15078163. 18: Trapani V, Patel V, Leong CO, Ciolino HP, Yeh GC, Hose C, Trepel JB, Stevens MF, Sausville EA, Loaiza-Pérez AI. DNA damage and cell cycle arrest induced by 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) is attenuated in aryl hydrocarbon receptor deficient MCF-7 cells. Br J Cancer. 2003 Feb 24;88(4):599-605. doi: 10.1038/sj.bjc.6600722. PMID: 12592376; PMCID: PMC2377159. 19: Leong CO, Gaskell M, Martin EA, Heydon RT, Farmer PB, Bibby MC, Cooper PA, Double JA, Bradshaw TD, Stevens MF. Antitumour 2-(4-aminophenyl)benzothiazoles generate DNA adducts in sensitive tumour cells in vitro and in vivo. Br J Cancer. 2003 Feb 10;88(3):470-7. doi: 10.1038/sj.bjc.6600719. PMID: 12569393; PMCID: PMC2747538. 20: Bradshaw TD, Trapani V, Vasselin DA, Westwell AD. The aryl hydrocarbon receptor in anticancer drug discovery: friend or foe? Curr Pharm Des. 2002;8(27):2475-90. doi: 10.2174/1381612023392784. PMID: 12369945.

View History

Clocortolone

MedKoo CAT#: 317550

CAS#: 4828-27-7 (free base)