| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
CYP1A1 (prodrug activation). [1]
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|---|---|
| ln Vitro |
In rat precision-cut lung slices (PCLS), NSC 710305 caused concentration-dependent increases in proinflammatory cytokine content. At 25 μM for 72 h, tissue levels of IL-1β, IL-5, and CINC increased; TNF-α was modestly elevated within 24 h (average 25 pg/mg protein). At 50 and 100 μM, significant increases were observed for IL-1β, IL-4, IL-5, TNF-α, IFN-γ, and CINC. CINC showed the largest increase from ~165 pg/mg protein in controls to ~44,000 pg/mg protein after 72 h exposure to 100 μM. IL-1β and IL-5 also showed large fold increases. Released cytokines in conditioned medium were measurable only at 100 μM. Protein content decreased significantly at 50 and 100 μM (maximum ~5-fold decrease at 100 μM for 72 h). Histological examination revealed concentration-dependent tissue destruction, decreased alveolar and bronchiolar cellularity, pyknotic nuclei, and increased ED-1(+) activated macrophages (e.g., at 25 μM, ED-1 score 53.8±4.5 vs control 32.0±3.0). After 72 h exposure, reversibility of toxicity was observed only at 25 μM following a 24 h recovery period (IL-5 and CINC decreased significantly, IL-5 fell to control levels ~60 pg/mg protein). At 50 and 100 μM, cytokine levels continued to rise during the recovery period. The no-observable adverse effect level (NOAEL) for 24, 48, and 72 h exposures was established as 10 μM. [1]
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| ln Vivo |
In mice, the maximal tolerated dose (MTD) of NSC 710305 was 120 mg/m² (20 mg/kg/day on days 1 and 8), which decreased lung:body and kidney:body weight ratios and increased serum alkaline phosphatase, indicating hepatic toxicity. In dogs, a 1-hour infusion of 80 mg/m² achieved plasma drug levels within the efficacious range based on in vitro data and caused gastrointestinal toxicity and neutropenia; a dose 3.5 times higher produced substantial pulmonary, bone marrow, and hepatic toxicity. In nonhuman primates, 1-hour infusions of 60 mg/m² produced no evidence of pulmonary toxicity, but increasing the dose to 80 mg/m² resulted in severe pulmonary toxicity and death within 24 hours. [1]
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| Cell Assay |
Precision-cut lung slices (PCLS) were prepared from male Fischer 344 rat lungs. Lungs were filled with 0.4% low-melting agarose in PBS at ~37°C, solidified in ice-cold PBS, then transferred to ice-cold Viaspan supplemented with 3 mM glutathione. Lobes were cored into 8 mm diameter cylinders and sliced into ~500-μm-thick disks using a Krumdieck slicer. Uniform slices were placed on sterile HATF paper inside titanium inserts. Slices were cultured in scintillation vials containing 1.7 mL Medium 199 supplemented with 288 U/L Humulin N, 100 μg/L hydrocortisone 21-acetate, 100 μg/L retinoic acid, and antibiotic-antimycotic solution. Vials were capped with PTFE membrane filters and placed in a roller drum (6-7 rpm) inside a humidified incubator at 37°C with 95% air/5% CO2. Medium was changed every 24 h. Drug treatment began on culture day 3 (48 h after initiating cultures) to allow resolution of slicing-induced cytokine response. NSC 710305 was added as 1:1000 dilutions from DMSO stocks; vehicle control received 0.1% DMSO. Conditioned medium was harvested every 24 h and replaced with fresh drug-containing medium. At indicated time points (24, 48, 72 h of exposure), slices were harvested for analysis of cytokines, protein content, and histology. For reversibility assessment, after 72 h exposure slices were cultured for an additional 24 h in drug-free medium. [1]
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| Animal Protocol |
In mice, an intravenous dose of 10 mg/kg NSC 710305 yielded a Cmax of 2.3 μM/h with no significant toxic effects (as referenced in discussion). [1]
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| ADME/Pharmacokinetics |
In rat PCLS, the no-observable adverse effect level (NOAEL) for 24, 48, and 72 h exposures was 10 μM NSC 710305. At 25 μM, modest increases in TNF-α (25 pg/mg protein) and reversible increases in IL-1β, IL-5, and CINC were observed. At 50 and 100 μM, significant and progressive tissue damage occurred, including decreased protein content (up to 5-fold), destruction of alveolar architecture, nuclear shrinkage, loss of cellularity, and increased ED-1(+) activated macrophages (scores ~53-57 vs control ~32). At 100 μM, IL-1β reached 1356 pg/mg protein, CINC 43,908 pg/mg protein after 72 h. After a 24 h recovery period, toxicity at 50 and 100 μM was irreversible with continued rise in cytokine levels (e.g., IL-1β increased from 323 to 479 pg/mg protein at 50 μM, and from 1356 to 2926 pg/mg protein at 100 μM). In vivo, mouse MTD (120 mg/m²) caused decreased lung:body and kidney:body weight ratios and increased serum alkaline phosphatase. In dogs, 80 mg/m² caused gastrointestinal toxicity and neutropenia; higher dose caused pulmonary, bone marrow, and hepatic toxicity. In nonhuman primates, 80 mg/m² caused severe pulmonary toxicity and death within 24 h. [1]
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| Toxicity/Toxicokinetics |
NSC 710305 (Phortress) is a P450 CYP1A1-activated antitumor prodrug. Cytotoxicity in sensitive cell lines (e.g., MCF-7 breast cancer cells) is governed by CYP1A1 metabolism and subsequent production of reactive metabolites that form DNA adducts. Insensitive cell lines (e.g., MDA-MB-435) lack CYP1A1 and are resistant. CYP1A1 expression in lung is inducible in rats, dogs, monkeys, and humans, raising concern for pulmonary toxicity. The PCLS model demonstrated that drug-induced inflammatory cytokine response (IL-1β, CINC, TNF-α, etc.) preceded tissue damage, and that high concentrations induced IFN-γ (a chronic inflammatory mediator) and IL-4 (anti-inflammatory cytokine) in addition to acute mediators. Hydrocortisone in the culture medium did not block the inflammatory response to NSC 710305. [1]
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| References |
| Molecular Formula |
C20H23N4OFS.2[HCL]
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|---|---|
| Molecular Weight |
459.4081
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| Exact Mass |
458.111
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| CAS # |
328087-38-3
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| Related CAS # |
328087-38-3 (HCl);741241-36-1 (free);
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| PubChem CID |
9804228
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
497
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=CC(=C1)C2=NC3=C(S2)C=CC(=C3)F)NC(=O)[C@H](CCCCN)N.Cl.Cl
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| InChi Key |
QZSMNTOCJVVFEU-CKUXDGONSA-N
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| 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
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| Chemical Name |
(S)-2,6-diamino-N-(4-(5-fluorobenzo[d]thiazol-2-yl)-2-methylphenyl)hexanamide dihydrochloride
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| Synonyms |
NSC-710305; 5F-DF-203 L-lysinamide; NSC-710305; NSC-710305; 5FDF 203 Llysinamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~272.09 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1767 mL | 10.8835 mL | 21.7670 mL | |
| 5 mM | 0.4353 mL | 2.1767 mL | 4.3534 mL | |
| 10 mM | 0.2177 mL | 1.0884 mL | 2.1767 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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