CCF-642
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MedKoo CAT#: 407472

CAS#: 346640-08-2

Description: CCF-642 is a protein disulfide isomerase (PDI) inhibitor. CCF642 exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib.

Chemical Structure

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CCF-642
CAS# 346640-08-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 407472
Name: CCF-642
CAS#: 346640-08-2
Chemical Formula: C15H10N2O4S3
Exact Mass: 377.98
Molecular Weight: 378.440
Elemental Analysis: C, 47.61; H, 2.66; N, 7.40; O, 16.91; S, 25.42

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 220 Ready to ship
50mg USD 380 Ready to ship
100mg USD 700 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3650 Ready to ship
2g USD 6450 Ready to ship
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Synonym: CCF-642; CCF 642; CCF642.

IUPAC/Chemical Name: 3-(4-Methoxyphenyl)-5-[(5-nitro-2-thienyl)methylene]-2-thioxo-4-thiazolidinone

InChi Key: SPYIETQLOVDJCF-XYOKQWHBSA-N

InChi Code: InChI=1S/C15H10N2O4S3/c1-21-10-4-2-9(3-5-10)16-14(18)12(24-15(16)22)8-11-6-7-13(23-11)17(19)20/h2-8H,1H3/b12-8+

SMILES Code: O=C1N(C2=CC=C(OC)C=C2)C(S/C1=C/C3=CC=C([N+]([O-])=O)S3)=S

Appearance: Brown 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: Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer

Biological target: CCF642 is a potent protein disulfide isomerases (PDI) inhibitor with an IC50 of 2.9 μM.
In vitro activity: C2C12 myoblasts were treated with CCF642, a novel specific small molecule inhibitor of protein disulfide isomerase (Vatolin et al., 2016). Apoptotic assay results indicated that the percentage of cisplatin‐induced apoptotic cells decreased in a dose‐dependent manner treated with CCF642. After concomitant incubation with 35 μM cisplatin for 24 h, the total apoptotic percentages of apoptotic cells in C2C12 myoblasts treated with 0.1% DMSO (vehicle control) reached 38.67%. Treatment of 3 μM CCF642 significantly reduced apoptotic rates to 5.17%. With the increase of drug concentration to 5 μM, the percentage of apoptotic cells dropped to 1.73% (Figure 6, a and b, P < 0.0001). The similar tendency was also observed in L6 rat myoblasts after treatment with CCF642 (Fig. S9, P = 0.0013 when CCF642 concentration is 3 μM; P = 0.001 when CCF642 concentration is 5 μM). These results indicated that CCF642 showed antiapoptotic effects on cisplatin‐induced C2C12 myoblasts. Furthermore, in differentiated C2C12 myotubes induced by cisplatin, treatment with CCF642 increased myotube diameter, elevated expression level of MHC and decreased levels of MURF1 and LC3 (Fig. S10A‐C). Reference: J Extracell Vesicles. 2021 Mar; 10(5): e12060. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944388/
In vivo activity: The YES2 model of ESCC‐associated cachexia was used to test the effect of CCF642 on prevention of muscle wasting in vivo. YES2 cells were subcutaneously implanted into nude mice. Ten days later, when tumour volume reached to 50 mm3, CCF642 (10 mg/kg) or albumin vehicle concomitant with cisplatin (5 mg/kg) were intraperitoneally (i.p.) administrated into nude mice. The treatment was three times a week for 4 weeks. Administration of CCF642 prevented body weight loss (Figure 6d, P = 0.003). However, CCF642 treatment did not result in changes in tumour volume during the experimental period (Figure 6e). CCF642 treatment also prevented cachectic muscle wasting (Figure 6, f and g, P = 0.0002), increased MHC protein level and downregulated the protein levels of MURF1 and LC3 in GA muscle as compared to albumin vehicle (Figure 6h). Moreover, adipocyte triglyceride (TG) content in eWAT was higher in response to CCF642 treatment with cisplatin than albumin with cisplatin (Fig. S10D). Histopathological analysis of eWAT revealed that CCF642 treatment prevented adipose tissues wasting (Fig. S10E). In addition, CCF642 treatment could prevent inflammation events (Fig. S10F‐I). Furthermore, body weight, GA muscle weight, tumour volume and H&E analysis supplemented with the pair‐fed group and CCF642 treatment alone group were compared. It was proved that CCF642 had no apparent toxicity (Fig. S11). In vivo results show that CCF642 is a promising drug candidate for cachexia treatment in ESCC. Reference: J Extracell Vesicles. 2021 Mar; 10(5): e12060. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944388/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 14.4 38.05

Preparing Stock Solutions

The following data is based on the product molecular weight 378.44 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.

Recalculate based on batch purity %
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. Gao X, Wang Y, Lu F, Chen X, Yang D, Cao Y, Zhang W, Chen J, Zheng L, Wang G, Fu M, Ma L, Song Y, Zhan Q. Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH/Bcl-2/caspase-3 pathway. J Extracell Vesicles. 2021 Mar;10(5):e12060. doi: 10.1002/jev2.12060. Epub 2021 Mar 10. PMID: 33732415; PMCID: PMC7944388. 1. Vatolin S, Phillips JG, Jha BK, Govindgari S, Hu J, Grabowski D, Parker Y, Lindner DJ, Zhong F, Distelhorst CW, Smith MR, Cotta C, Xu Y, Chilakala S, Kuang RR, Tall S, Reu FJ. Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma. Cancer Res. 2016 Jun 1;76(11):3340-50. doi: 10.1158/0008-5472.CAN-15-3099. Epub 2016 Apr 6. PMID: 27197150.
In vitro protocol: 1. Gao X, Wang Y, Lu F, Chen X, Yang D, Cao Y, Zhang W, Chen J, Zheng L, Wang G, Fu M, Ma L, Song Y, Zhan Q. Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH/Bcl-2/caspase-3 pathway. J Extracell Vesicles. 2021 Mar;10(5):e12060. doi: 10.1002/jev2.12060. Epub 2021 Mar 10. PMID: 33732415; PMCID: PMC7944388. 1. Vatolin S, Phillips JG, Jha BK, Govindgari S, Hu J, Grabowski D, Parker Y, Lindner DJ, Zhong F, Distelhorst CW, Smith MR, Cotta C, Xu Y, Chilakala S, Kuang RR, Tall S, Reu FJ. Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma. Cancer Res. 2016 Jun 1;76(11):3340-50. doi: 10.1158/0008-5472.CAN-15-3099. Epub 2016 Apr 6. PMID: 27197150.
In vivo protocol: 1. Gao X, Wang Y, Lu F, Chen X, Yang D, Cao Y, Zhang W, Chen J, Zheng L, Wang G, Fu M, Ma L, Song Y, Zhan Q. Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH/Bcl-2/caspase-3 pathway. J Extracell Vesicles. 2021 Mar;10(5):e12060. doi: 10.1002/jev2.12060. Epub 2021 Mar 10. PMID: 33732415; PMCID: PMC7944388.

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1: Vatolin S, Phillips JG, Jha BK, Govindgari S, Hu J, Grabowski D, Parker Y, Lindner DJ, Zhong F, Distelhorst CW, Smith MR, Cotta C, Xu Y, Chilakala S, Kuang RR, Tall S, Reu FJ. Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma. Cancer Res. 2016 Jun1 ; 76(11):3340-50. doi: 10.1158/0008-5472.CAN-15-3099. Epub 2016 Apr 6. PubMed PMID: 27197150.