PHORTRESS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H23FN4OS.2ClH
Molecular Weight	459.408
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.CC1=C(NC(=O)[C@@H](N)CCCCN)C=CC(=C1)C2=NC3=C(S2)C=CC(F)=C3

InChI

InChIKey=QZSMNTOCJVVFEU-CKUXDGONSA-N

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

HIDE SMILES / InChI

Molecular Formula	C20H23FN4OS
Molecular Weight	386.486
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15377855 | https://www.ncbi.nlm.nih.gov/pubmed/15634650
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800021353

5F-DF-203-L-LYSINAMIDE (Phortress) is an experimental antitumor agent with potent and selective activity against human-derived carcinomas of breast, ovarian and renal origin. The mechanism of action of Phortress is distinct from all classes of chemotherapeutic agents currently in the clinic, and involves metabolic activation by cytochrome P450 (CYP) 1A1 to electrophilic species, which generate DNA adducts in sensitive tumors only. Phortress is in phase I clinical trials for the treatment of solid tumours. The compound was co-developed by Pharminox, University of Nottingham and Cancer Research UK.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: http://adisinsight.springer.com/drugs/800021353 \| https://www.ncbi.nlm.nih.gov/pubmed/23143926 \| https://www.ncbi.nlm.nih.gov/pubmed/15634650	Crosslinking Agent 81
Cytochrome P450 1A1 31 Target ID: CHEMBL2231 Sources: http://conference.ncri.org.uk/abstracts/2012/abstracts/LB79.html \| http://adisinsight.springer.com/drugs/800021353 \| https://www.ncbi.nlm.nih.gov/pubmed/12592376 \| https://www.ncbi.nlm.nih.gov/pubmed/15377855	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: http://conference.ncri.org.uk/abstracts/2012/abstracts/LB79.html http://adisinsight.springer.com/drugs/800021353	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.31 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19088497	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PHORTRESS plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.27 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19088497	10 mg/kg 1 times / week multiple, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHORTRESS plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3.239 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19088497	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PHORTRESS plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.415 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19088497	10 mg/kg 1 times / week multiple, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHORTRESS plasma	Mus musculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

50 patients were treated with 145 cycles of 5F-DF-203-L-LYSINAMIDE (Phortress) over a dose range of 3-50mg/m2. The first 6 patients were treated on d1,8 Q4weeks, 2 patients having DLTs. The protocol was amended to d1 q3weekly dosing, and escalated from 3 to 50 mg/m2 over 10 cohorts.

Route of Administration: Intravenous

In Vitro Use Guide

5F-DF-203-L-LYSINAMIDE caused a concentration-dependent cytokine response in precision-cut lung slice (PCLS) model. Exposure to 25uM 5F-DF-203-L-LYSINAMIDE modestly elevated TNF-α within 24h, with average levels of TNF-α in PCLS reaching 25 pg/mg, just above assay LLOD. Exposure to 25uM 5F-DF-203-L-LYSINAMIDE for 72h increased tissue levels of IL-β, IL-5, and CINC. Exposure to 50 and 100uM caused significant increases in PCLS content for all six cytokines analyzed.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:18:26 GMT 2023` Edited by `admin` on `Sat Dec 16 11:18:26 GMT 2023`
Record UNII	AXR52N9SMF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PHORTRESS

Common Name

English

NSC-710305

Code

English

5F-DF-203-L-LYSINAMIDE DIHYDROCHLORIDE

Common Name

English

HEXANAMIDE, 2,6-DIAMINO-N-(4-(5-FLUORO-2-BENZOTHIAZOLYL)-2-METHYLPHENYL)-, HYDROCHLORIDE (1:2), (2S)-

Systematic Name

English

(2S)-2,6-DIAMINO-N-(4-(5-FLUORO-1,3-BENZOTHIAZOL-2-YL)-2-METHYL-PHENYL)HEXANAMIDE HYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

CAS

328087-38-3