| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| 50mg | |||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
FGF3 (Kd = 15.9 μM); FGF8b (Kd = 18.9 μM); FGF22 (Kd = 26.8 μM); FGF20 (Kd = 29.4 μM); FGF2/FGFR (IC50 = 30 μM)
FGF2/FGFR interaction (IC50 ≈ 30 µM); FGF3 (Kd = 15.9 µM); FGF8b (Kd = 18.9 µM); FGF22 (Kd = 26.8 µM); FGF20 (Kd = 29.4 µM) |
|---|---|
| ln Vitro |
NSC12 suppresses angiogenesis, metastases, and tumor growth that is FGF-dependent. While FGF2 does not interact with heparin when bound to the immobilized receptor (ID50 ~30 μM), NSC12 prevents this from happening. NSC12 disrupts the FGF2/FGFR1 interaction while leaving the growth factor unaffected in its interactions with heparin or HSPGs. Moreover, immobilized FGF3, FGF4, FGF6, FGF8, FGF16, FGF18, FGF20, and FGF22 are bound by NSC12, with Kd values varying from approximately ~16 and ~120 μM. Through interactions with every member of the canonical FGF subfamilies, NSC12 may function as a multi-FGF trap. NSC12 inhibits Chinese hamster ovary (CHO) cells that express Klotho from activating FGFR1 through FGF23. All tumor cell lines treated with NSC12 exhibit a reduction in the S phase of the cell cycle; however, LLC cells exhibit an accumulation in the S phase. In CHO cell transfectants, NSC12 inhibits the phosphorylation of FGFR1, FGFR2, FGFR3, and FGFR4. With no inhibitory effect on FGF-independent cancer cell lines or HCC827 cancer cells that carry a tumor-driving mutation of the EGFR TK domain, NSC12 suppresses the growth of a variety of FGF-dependent murine and human cancer cell lines[1].
NSC12 inhibits FGF2 binding to immobilized receptor with an IC50 of approximately 30 µM without affecting FGF2 interaction with heparin or HSPGs. It binds to immobilized FGF3, FGF4, FGF6, FGF8, FGF16, FGF18, FGF20, and FGF22 with Kd values ranging from 16–120 µM. NSC12 inhibits FGFR1, FGFR2, FGFR3, and FGFR4 phosphorylation in CHO cell transfectants. It suppresses proliferation of various FGF-dependent murine and human cancer cell lines without affecting FGF-independent cancer cells or HCC827 cells with EGFR TK domain mutation. The compound's ability to bind multiple FGFs with high affinity makes it a pan-FGF trap that can broadly inhibit FGF/FGFR signaling. |
| ln Vivo |
In FGF-dependent murine and human tumor models, parenteral and oral administration of NSC12 inhibits FGFR activation, tumor growth, angiogenesis, and metastasis. At all doses examined in the animal models, NSC12 significantly reduces tumor weight, tumor cell FGFR1 phosphorylation and proliferation, and tumor CD31+ neovascularization[1].
NSC12 inhibits FGFR activation, tumor growth, angiogenesis, and metastasis in FGF-dependent murine and human tumor models following both parenteral and oral administration. It significantly reduces tumor weight, tumor cell FGFR1 phosphorylation, proliferation, and CD31+ microvessel formation in animal models. Importantly, no systemic toxic effects are observed at all doses examined. The compound's oral availability and efficacy in multiple tumor models support its potential as a therapeutic agent for FGF-dependent cancers. |
| Enzyme Assay |
FGF binding affinity is measured using surface plasmon resonance or ELISA-based binding assays with immobilized FGF proteins to determine Kd values. FGFR phosphorylation is assessed by Western blot using phospho-specific antibodies against FGFR1-4. FGF2/FGFR interaction inhibition is measured using competition binding assays with labeled FGF2 and immobilized FGFR1. The compound's ability to inhibit the formation of the bioactive HSPG/FGF/FGFR ternary complex is also assessed.
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| Cell Assay |
In 96 well plates, KATO Ⅲ cells are plated at 104 cells/well in RPMI medium supplemented with 1% FBS. Following a 24-hour period, cells are exposed to varying concentrations of FGFs (30 ng/ml) with or without an ideal dosage of NSC12 (1.0 or 3.0 μM) or NSC21. The MTT assay is carried out in accordance with the manufacturer's instructions after 72 hours. With a plate reader set to a reference wavelength of 630 nm and a test wavelength of 595 nm, the optical density (OD) is calculated.
Cell proliferation is assessed in various FGF-dependent tumor cell lines (murine and human) using MTT or CellTiter-Glo assays after treatment with NSC12. Effects on cell cycle distribution are analyzed by flow cytometry. FGFR phosphorylation is measured in CHO cell transfectants expressing different FGFRs. FGF23-mediated FGFR1 activation is assessed in Klotho-expressing CHO cells. The compound's selectivity for FGF-dependent cancer cells over FGF-independent cells is confirmed in these assays. |
| Animal Protocol |
C57BL/6 mice
from 2.5 to 10 mg/kg i.p. In FGF-dependent murine and human tumor models, NSC12 is administered via injection or oral routes. Tumor growth, angiogenesis (CD31 staining), and metastasis are assessed. FGFR phosphorylation is measured in tumor tissues. In animal models, NSC12 treatment shows significant reductions in tumor weight, FGFR1 phosphorylation, proliferation markers, and CD31+ microvessel formation. No systemic toxic effects are observed at all doses examined. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for NSC-12 are limited. The compound is orally available and has been shown to be effective following both oral and parenteral administration in vivo. It is soluble in DMSO (96 mg/mL) and ethanol (63 mg/mL) for formulation. Detailed PK parameters such as half-life, bioavailability, and tissue distribution have not been extensively reported. The compound's oral bioavailability supports its potential for therapeutic development.
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| Toxicity/Toxicokinetics |
NSC12 shows no systemic toxic effects at all doses examined in animal models. Comprehensive toxicology data are limited as the compound remains in preclinical development. Standard laboratory safety precautions should be observed during handling. The compound has not been evaluated in formal toxicology studies for human use. The compound has not entered clinical trials.
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| References | |
| Additional Infomation |
NCS172285 is a 3β-hydroxy steroid with the structure androst-5-en-3β-ol, in which the 17β-hydrogen is replaced by a 1,3-dihydroxy-3,3-bis(trifluoromethyl)propyl group. NCS172285 (also known as NSC12) has been used as an extracellular fibroblast growth factor (FGF) scavenger, showing promise in cancer treatment. The stereochemical structure shown in the figure represents the most active stereoisomer, determined by Mattia Anselmi (PhD dissertation, University of Parma, 2015). It is a 20-hydroxy steroid, a fluorinated steroid, and a 3β-hydroxy-Δ5-steroid.
NSC12 is an extracellular FGF trap with significant implications in cancer therapy. It functions as a multi-FGF trap by interacting with every member of the canonical FGF subfamily. The compound represents a novel approach to targeting FGF-dependent tumors by sequestering FGFs in the extracellular space rather than inhibiting FGFRs intracellularly. NSC12 has been shown to inhibit the growth and progression of several FGF-dependent tumor models, including multiple myeloma. It has not entered clinical trials and remains a research tool for studying FGF biology and FGF-dependent cancers. |
| Molecular Formula |
C24H34F6O3
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|---|---|---|
| Molecular Weight |
484.52
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| Exact Mass |
484.241
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| Elemental Analysis |
C, 59.49; H, 7.07; F, 23.53; O, 9.91
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| CAS # |
102586-30-1
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| Related CAS # |
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| PubChem CID |
97290924
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| Appearance |
White to light yellow solid powder
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| LogP |
5.533
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
33
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| Complexity |
778
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| Defined Atom Stereocenter Count |
8
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| SMILES |
OC1CC[C@@]2([C@H]3CC[C@@]4([C@@H](C(CC(C(F)(F)F)(O)C(F)(F)F)O)CC[C@H]4[C@@H]3CC=C2C1)C)C
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| InChi Key |
OHKBOEWLASAFLW-DRPHTYIMSA-N
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| InChi Code |
InChI=1S/C24H34F6O3/c1-20-9-7-14(31)11-13(20)3-4-15-16-5-6-18(21(16,2)10-8-17(15)20)19(32)12-22(33,23(25,26)27)24(28,29)30/h3,14-19,31-33H,4-12H2,1-2H3/t14?,15-,16-,17-,18+,19?,20-,21-/m0/s1
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| Chemical Name |
4,4,4-trifluoro-1-[(8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-3-(trifluoromethyl)butane-1,3-diol
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0639 mL | 10.3195 mL | 20.6390 mL | |
| 5 mM | 0.4128 mL | 2.0639 mL | 4.1278 mL | |
| 10 mM | 0.2064 mL | 1.0319 mL | 2.0639 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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