Regorafenib
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MedKoo CAT#: 202436

CAS#: 755037-03-7

Description: Regorafenib, also known as BAY 73-4506; binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. Regorafenib demonstrated to increase the overall survival of patients with metastatic colorectal cancer.

Chemical Structure

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Regorafenib
CAS# 755037-03-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 202436
Name: Regorafenib
CAS#: 755037-03-7
Chemical Formula: C21H15ClF4N4O3
Exact Mass: 482.08
Molecular Weight: 482.815
Elemental Analysis: C, 52.24; H, 3.13; Cl, 7.34; F, 15.74; N, 11.60; O, 9.94

Price and Availability

Size Price Availability Quantity
50mg USD 90 Ready to ship
100mg USD 150 Ready to ship
200mg USD 250 Ready to ship
500mg USD 550 Ready to ship
1g USD 950 Ready to ship
2g USD 1650 Ready to ship
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Related CAS #: 755037-03-7   1019206-88-2 (hydrate)    

Synonym: BAY 734506; BAY734506; BAY-734506; Regorafenib. trade name: Stivarga.

IUPAC/Chemical Name: 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide

InChi Key: ZFLJHSQHILSNCM-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H27N7O/c1-2-4-15(5-3-1)24-20-18-19(23-14-22-18)26-21(27-20)25-16-6-8-17(9-7-16)28-10-12-29-13-11-28/h6-9,14-15H,1-5,10-13H2,(H3,22,23,24,25,26,27)

SMILES Code: C12=NC(NC3=CC=C(N4CCOCC4)C=C3)=NC(NC5CCCCC5)=C1NC=N2

Appearance: Off-white to light pink 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, not in water

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:    

Biological target: Regorafenib (BAY 73-4506) is a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively.
In vitro activity: Regorafenib acts as a inhibitor of EGFR signaling that attenuated the activation of EGFR and EGFR related downstream signaling cascades in colorectal cancer. This study’s results suggested that the suppression of EGFR signaling was associated with regorafenib-inhibited progression of colorectal cancer. Reference: Biomed Pharmacother. 2020 Aug;128:110319. https://pubmed.ncbi.nlm.nih.gov/32502841/
In vivo activity: This study found that regorafenib may enhance antitumor immunity through modulation of macrophage polarization, independent of its anti-angiogenic effects. Optimization of regorafenib dosage for rational design of combination therapy regimen may improve the therapeutic index in the clinic. Reference: J Immunother Cancer. 2021; 9(3): e001657. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986673/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 62.14
Ethanol 14.0 30.00
DMSO 128.7 266.50

Preparing Stock Solutions

The following data is based on the product molecular weight 482.82 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. Liu YC, Tsai JJ, Weng YS, Hsu FT. Regorafenib suppresses epidermal growth factor receptor signaling-modulated progression of colorectal cancer. Biomed Pharmacother. 2020 Aug;128:110319. doi: 10.1016/j.biopha.2020.110319. Epub 2020 Jun 2. PMID: 32502841. 2. Subramonian D, Phanhthilath N, Rinehardt H, Flynn S, Huo Y, Zhang J, Messer K, Mo Q, Huang S, Lesperance J, Zage PE. Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways. Br J Cancer. 2020 Aug;123(4):568-579. doi: 10.1038/s41416-020-0905-8. Epub 2020 May 27. PMID: 32457362; PMCID: PMC7434894. 3. Ou DL, Chen CW, Hsu CL, Chung CH, Feng ZR, Lee BS, Cheng AL, Yang MH, Hsu C. Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages. J Immunother Cancer. 2021 Mar;9(3):e001657. doi: 10.1136/jitc-2020-001657. PMID: 33753566; PMCID: PMC7986673. 4. Li X, Ma L, Huang K, Wei Y, Long S, Liu Q, Zhang D, Wu S, Wang W, Yang G, Zhou H, Yang C. Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway. Int J Mol Sci. 2021 Feb 17;22(4):1985. doi: 10.3390/ijms22041985. PMID: 33671452; PMCID: PMC7922359.
In vitro protocol: 1. Liu YC, Tsai JJ, Weng YS, Hsu FT. Regorafenib suppresses epidermal growth factor receptor signaling-modulated progression of colorectal cancer. Biomed Pharmacother. 2020 Aug;128:110319. doi: 10.1016/j.biopha.2020.110319. Epub 2020 Jun 2. PMID: 32502841. 2. Subramonian D, Phanhthilath N, Rinehardt H, Flynn S, Huo Y, Zhang J, Messer K, Mo Q, Huang S, Lesperance J, Zage PE. Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways. Br J Cancer. 2020 Aug;123(4):568-579. doi: 10.1038/s41416-020-0905-8. Epub 2020 May 27. PMID: 32457362; PMCID: PMC7434894.
In vivo protocol: 1. Ou DL, Chen CW, Hsu CL, Chung CH, Feng ZR, Lee BS, Cheng AL, Yang MH, Hsu C. Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages. J Immunother Cancer. 2021 Mar;9(3):e001657. doi: 10.1136/jitc-2020-001657. PMID: 33753566; PMCID: PMC7986673. 2. Li X, Ma L, Huang K, Wei Y, Long S, Liu Q, Zhang D, Wu S, Wang W, Yang G, Zhou H, Yang C. Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway. Int J Mol Sci. 2021 Feb 17;22(4):1985. doi: 10.3390/ijms22041985. PMID: 33671452; PMCID: PMC7922359.

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1: Victorino APOS, Meton F, Mardegan L, Festa J, Piranda DN, Araujo KB. Trifluridine/tipiracil (FTD/TPI) and regorafenib in older patients with metastatic colorectal cancer. J Geriatr Oncol. 2023 May;14(4):101477. doi: 10.1016/j.jgo.2023.101477. Epub 2023 Mar 27. PMID: 36990929.


2: Khachatryan V, Muazzam A, Hamal C, Velugoti LSDR, Tabowei G, Gaddipati GN, Mukhtar M, Alzubaidee MJ, Dwarampudi RS, Mathew S, Bichenapally S, Mohammed L. The Role of Regorafenib in the Management of Advanced Gastrointestinal Stromal Tumors: A Systematic Review. Cureus. 2022 Sep 1;14(9):e28665. doi: 10.7759/cureus.28665. PMID: 36199644; PMCID: PMC9526434.


3: Blay JY, Duffaud F, George S, Maki RG, Penel N. Regorafenib for the Treatment of Sarcoma. Curr Treat Options Oncol. 2022 Nov;23(11):1477-1502. doi: 10.1007/s11864-022-00990-0. Epub 2022 Sep 30. PMID: 36178573.


4: Liu J, Tao H, Yuan T, Li J, Li J, Liang H, Huang Z, Zhang E. Immunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy. Front Immunol. 2022 Sep 2;13:992611. doi: 10.3389/fimmu.2022.992611. PMID: 36119072; PMCID: PMC9479218.


5: Akin Telli T, Bregni G, Vanhooren M, Saude Conde R, Hendlisz A, Sclafani F. Regorafenib in combination with immune checkpoint inhibitors for mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer. Cancer Treat Rev. 2022 Nov;110:102460. doi: 10.1016/j.ctrv.2022.102460. Epub 2022 Aug 27. PMID: 36058142.


6: De Felice M, De Marinis P, Martin G, Bruscella S, De Bellis A, Poliero L, Turitto G. Dramatic response to regorafenib in early glioblastoma progression: case report and review of the literature. Eur Rev Med Pharmacol Sci. 2022 Jul;26(14):5008-5013. doi: 10.26355/eurrev_202207_29287. PMID: 35916797.


7: Yin Q, Guo N, Zhou X, Xu H, Lei S, Fu P, Zhong H. Regorafenib-induced renal- limited thrombotic microangiopathy: a case report and review of literatures. BMC Nephrol. 2022 Mar 19;23(1):112. doi: 10.1186/s12882-021-02656-9. PMID: 35305559; PMCID: PMC8933930.


8: Xu X, Yu Y, Liu M, Liang L, Liu T. Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review. Transl Cancer Res. 2022 Jan;11(1):276-287. doi: 10.21037/tcr-20-3539. PMID: 35261903; PMCID: PMC8841594.


9: Shiri P, Ramezanpour S, Amani AM, Dehaen W. A patent review on efficient strategies for the total synthesis of pazopanib, regorafenib and lenvatinib as novel anti-angiogenesis receptor tyrosine kinase inhibitors for cancer therapy. Mol Divers. 2022 Oct;26(5):2981-3002. doi: 10.1007/s11030-022-10406-8. Epub 2022 Mar 2. PMID: 35235141.


10: Gaudino S, Marziali G, Giordano C, Gigli R, Varcasia G, Magnani F, Chiesa S, Balducci M, Costantini AM, Della Pepa GM, Olivi A, Russo R, Colosimo C. Regorafenib in Glioblastoma Recurrence: How to Deal With MR Imaging Treatments Changes. Front Radiol. 2022 Feb 25;1:790456. doi: 10.3389/fradi.2021.790456. PMID: 37492166; PMCID: PMC10365006.


11: Zhang Y, Zhang F, Zhao L, Fu X, Shang Y, Gao Q. Long-term survival of a patient with microsatellite-stable refractory colorectal cancer with regorafenib and PD-1 inhibitor sintilimab: a case report and review of literature. BMC Gastroenterol. 2021 Oct 23;21(1):399. doi: 10.1186/s12876-021-01950-y. PMID: 34688262; PMCID: PMC8542310.


12: Ouchi R, Okada K, Usui K, Kurata N, Suzuki S, Nagao M, Watanabe Y, Koyama K. Intestinal Perforation in a Patient with Colon Cancer during Treatment with Regorafenib: A Case Report and Review of the Literature. Tohoku J Exp Med. 2021 Jul;254(3):207-211. doi: 10.1620/tjem.254.207. PMID: 34321384.


13: Granito A, Forgione A, Marinelli S, Renzulli M, Ielasi L, Sansone V, Benevento F, Piscaglia F, Tovoli F. Experience with regorafenib in the treatment of hepatocellular carcinoma. Therap Adv Gastroenterol. 2021 May 28;14:17562848211016959. doi: 10.1177/17562848211016959. PMID: 34104211; PMCID: PMC8165525.


14: Granito A, Marinelli S, Forgione A, Renzulli M, Benevento F, Piscaglia F, Tovoli F. Regorafenib Combined with Other Systemic Therapies: Exploring Promising Therapeutic Combinations in HCC. J Hepatocell Carcinoma. 2021 May 26;8:477-492. doi: 10.2147/JHC.S251729. PMID: 34079777; PMCID: PMC8165211.


15: Papadimitriou M, Papadimitriou CA. Antiangiogenic Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: Focusing on Regorafenib. Anticancer Res. 2021 Feb;41(2):567-582. doi: 10.21873/anticanres.14809. PMID: 33517262.


16: Sahin IH, Tan E, Kim R. Regorafenib, an investigational agent for the treatment of cholangiocarcinoma. Expert Opin Investig Drugs. 2021 Apr;30(4):333-341. doi: 10.1080/13543784.2021.1867537. Epub 2020 Dec 30. PMID: 33378249.


17: Mohammadi M, Gelderblom H. Systemic therapy of advanced/metastatic gastrointestinal stromal tumors: an update on progress beyond imatinib, sunitinib, and regorafenib. Expert Opin Investig Drugs. 2021 Feb;30(2):143-152. doi: 10.1080/13543784.2021.1857363. Epub 2020 Dec 3. PMID: 33252274.


18: Loupakis F, Antonuzzo L, Bachet JB, Kuan FC, Macarulla T, Pietrantonio F, Xu RH, Taniguchi H, Winder T, Yuki S, Zeng S, Bekaii-Saab T. Practical considerations in the use of regorafenib in metastatic colorectal cancer. Ther Adv Med Oncol. 2020 Oct 31;12:1758835920956862. doi: 10.1177/1758835920956862. PMID: 33193826; PMCID: PMC7607787.


19: Yoshino T. Current and Future Research Into the Mechanism of Action of Regorafenib. Clin Adv Hematol Oncol. 2019 Aug;17 Suppl 12(8):14-16. PMID: 32720934.


20: Prager G. Implications of the Mechanism of Action of Regorafenib for Clinical Practice. Clin Adv Hematol Oncol. 2019 Aug;17 Suppl 12(8):5-13. PMID: 32720933.