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MedKoo Cat#: 206423 | Name: CC-223
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Onatasertib, also known as CC-223, is an orally available inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. mTOR kinase inhibitor CC-223 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, plays an important role downstream in the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in human cancers.

Chemical Structure

CC-223
CC-223
CAS#1228013-30-6

Theoretical Analysis

MedKoo Cat#: 206423

Name: CC-223

CAS#: 1228013-30-6

Chemical Formula: C21H27N5O3

Exact Mass: 397.2114

Molecular Weight: 397.48

Elemental Analysis: C, 63.46; H, 6.85; N, 17.62; O, 12.08

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 1,950.00 Ready to ship
1g USD 3,250.00 Ready to ship
2g USD 5,450.00 2 weeks
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Related CAS #
1228013-30-6
Synonym
CC-223; CC 223; CC223; Onatasertib; ATG-008; ATG008; ATG 008
IUPAC/Chemical Name
7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((1r,4r)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one
InChi Key
UFKLYTOEMRFKAD-SHTZXODSSA-N
InChi Code
InChI=1S/C21H27N5O3/c1-21(2,28)17-9-4-13(10-22-17)16-11-23-19-20(25-16)26(18(27)12-24-19)14-5-7-15(29-3)8-6-14/h4,9-11,14-15,28H,5-8,12H2,1-3H3,(H,23,24)/t14-,15-
SMILES Code
OC(C)(C)C(N=C1)=CC=C1C(N=C2N3[C@@H]4CC[C@H](CC4)OC)=CN=C2NCC3=O
Appearance
Red to 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:
CC-223 is an orally bioavailable inhibitor of mTOR kinase, with an IC50 value for mTOR kinase of 16 nM.
In vitro activity:
MTT assay results in Figure 1A demonstrated that CC223 inhibited ovarian cancer cell survival, in a concentration-dependent manner. The IC-50s of CC223 for SKOV3 cells and CaOV3 cells were 64.32 ± 5.21 nM and 88.17 ± 6.32 nM, respectively. On the other hand, treatment with CC223 at same concentration (10–300 nM) was yet non-cytotoxic to primary human ovarian surface epithelial (IOSE-80 line) cells (Figure 1A). To further study the activity of CC223 in ovarian cancer cells, clonogenicity assay was performed. Treatment with CC223 (30–300 nM) potently decreased the number of viable SKOV3 colonies (Figure 1B). Further studies showed that the percentage of trypan blue positive (“dead”) SKOV3 cells was significantly increased after CC223 (30–300 nM) treatment (Figure 1C). These results suggested that CC223 was cytotoxic to cultured human ovarian cancer cells. Reference: Oncotarget. 2017 Aug 29; 8(35): 58469–58479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601667/
In vivo activity:
Weekly tumor growth curve results in Fig 5A clearly showed that CC-223 oral administration dramatically inhibited HepG2 xenograft growth in SCID mice. CC-223 again displayed a dose-dependent activity in vivo. CC-223 at 30 mg/kg was more potent than 10 mg/kg in inhibiting HepG2 xenografts (Fig 5A). Results in Fig 5B showed that CC-223 administration didn’t affect the body weight of experimental mice, indicating that CC-223 regimens were apparently safe. To test signaling changes in vivo, at day-3, 12 hours after initial CC-223 administration, one tumor of each group was separated. Western blotting assay analyzing HepG2 tumor lysates showed that activation of mTORC1 (p-S6K1) and mTORC2 (p-AKT, Ser-473) were largely inhibited in tumor lysates with CC-223 administration (Fig 5C). ERK activation, tested by p-ERK1/2, was yet unchanged (Fig 5C). Thus, in line with the in vitro findings, oral administration of CC-223 similarly inhibited mTORC1/C2 activation in vivo. Reference: PLoS One. 2017; 12(3): e0173252. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363890/
Solvent mg/mL mM
Solubility
DMSO 43.7 109.87
DMF 30.0 75.48
DMF:PBS (pH 7.2) (1:1) 0.5 1.26
Ethanol 49.5 124.53
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 397.48 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. Jin Z, Niu H, Wang X, Zhang L, Wang Q, Yang A. Preclinical study of CC223 as a potential anti-ovarian cancer agent. Oncotarget. 2017 May 10;8(35):58469-58479. doi: 10.18632/oncotarget.17753. PMID: 28938571; PMCID: PMC5601667. 2. Mortensen DS, Fultz KE, Xu S, Xu W, Packard G, Khambatta G, Gamez JC, Leisten J, Zhao J, Apuy J, Ghoreishi K, Hickman M, Narla RK, Bissonette R, Richardson S, Peng SX, Perrin-Ninkovic S, Tran T, Shi T, Yang WQ, Tong Z, Cathers BE, Moghaddam MF, Canan SS, Worland P, Sankar S, Raymon HK. CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization. Mol Cancer Ther. 2015 Jun;14(6):1295-305. doi: 10.1158/1535-7163.MCT-14-1052. Epub 2015 Apr 8. PMID: 25855786. 3. Orr-Asman MA, Chu Z, Jiang M, Worley M, LaSance K, Koch SE, Carreira VS, Dahche HM, Plas DR, Komurov K, Qi X, Mercer CA, Anthony LB, Rubinstein J, Thomas HE. mTOR Kinase Inhibition Effectively Decreases Progression of a Subset of Neuroendocrine Tumors that Progress on Rapalog Therapy and Delays Cardiac Impairment. Mol Cancer Ther. 2017 Nov;16(11):2432-2441. doi: 10.1158/1535-7163.MCT-17-0058. Epub 2017 Sep 1. PMID: 28864682. 4. Xie Z, Wang J, Liu M, Chen D, Qiu C, Sun K. CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo. PLoS One. 2017 Mar 23;12(3):e0173252. doi: 10.1371/journal.pone.0173252. PMID: 28334043; PMCID: PMC5363890.
In vitro protocol:
1. Jin Z, Niu H, Wang X, Zhang L, Wang Q, Yang A. Preclinical study of CC223 as a potential anti-ovarian cancer agent. Oncotarget. 2017 May 10;8(35):58469-58479. doi: 10.18632/oncotarget.17753. PMID: 28938571; PMCID: PMC5601667. 2. Mortensen DS, Fultz KE, Xu S, Xu W, Packard G, Khambatta G, Gamez JC, Leisten J, Zhao J, Apuy J, Ghoreishi K, Hickman M, Narla RK, Bissonette R, Richardson S, Peng SX, Perrin-Ninkovic S, Tran T, Shi T, Yang WQ, Tong Z, Cathers BE, Moghaddam MF, Canan SS, Worland P, Sankar S, Raymon HK. CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization. Mol Cancer Ther. 2015 Jun;14(6):1295-305. doi: 10.1158/1535-7163.MCT-14-1052. Epub 2015 Apr 8. PMID: 25855786.
In vivo protocol:
1. Orr-Asman MA, Chu Z, Jiang M, Worley M, LaSance K, Koch SE, Carreira VS, Dahche HM, Plas DR, Komurov K, Qi X, Mercer CA, Anthony LB, Rubinstein J, Thomas HE. mTOR Kinase Inhibition Effectively Decreases Progression of a Subset of Neuroendocrine Tumors that Progress on Rapalog Therapy and Delays Cardiac Impairment. Mol Cancer Ther. 2017 Nov;16(11):2432-2441. doi: 10.1158/1535-7163.MCT-17-0058. Epub 2017 Sep 1. PMID: 28864682. 2. Xie Z, Wang J, Liu M, Chen D, Qiu C, Sun K. CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo. PLoS One. 2017 Mar 23;12(3):e0173252. doi: 10.1371/journal.pone.0173252. PMID: 28334043; PMCID: PMC5363890.
1: Wang JY, Jin X, Zhang X, Li XF. CC-223 inhibits human head and neck squamous cell carcinoma cell growth. Biochem Biophys Res Commun. 2018 Feb 19;496(4):1191-1196. doi: 10.1016/j.bbrc.2018.01.168. Epub 2018 Jan 31. PMID: 29402408. 2: Ribrag V, Chavez JC, Boccomini C, Kaplan J, Chandler JC, Santoro A, Corradini P, Flinn IW, Advani R, Cassier PA, Sangha R, Kenkre VP, Isufi I, Uttamsingh S, Hagner PR, Gandhi AK, Shen F, Michelliza S, Haeske H, Hege K, Pourdehnad M, Kuruvilla J. Phase Ib study of combinations of avadomide (CC-122), CC-223, CC-292, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma. EJHaem. 2022 Jan 14;3(1):139-153. doi: 10.1002/jha2.375. PMID: 35846221; PMCID: PMC9176062. 3: Xie Z, Wang J, Liu M, Chen D, Qiu C, Sun K. CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo. PLoS One. 2017 Mar 23;12(3):e0173252. doi: 10.1371/journal.pone.0173252. PMID: 28334043; PMCID: PMC5363890. 4: Mortensen DS, Fultz KE, Xu S, Xu W, Packard G, Khambatta G, Gamez JC, Leisten J, Zhao J, Apuy J, Ghoreishi K, Hickman M, Narla RK, Bissonette R, Richardson S, Peng SX, Perrin-Ninkovic S, Tran T, Shi T, Yang WQ, Tong Z, Cathers BE, Moghaddam MF, Canan SS, Worland P, Sankar S, Raymon HK. CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization. Mol Cancer Ther. 2015 Jun;14(6):1295-305. doi: 10.1158/1535-7163.MCT-14-1052. Epub 2015 Apr 8. PMID: 25855786. 5: Guo Y, Zhu H, Weng M, Zhang H, Wang C, Sun L. CC-223, NSC781406, and BGT226 Exerts a Cytotoxic Effect Against Pancreatic Cancer Cells via mTOR Signaling. Front Pharmacol. 2020 Nov 11;11:580407. doi: 10.3389/fphar.2020.580407. PMID: 33343350; PMCID: PMC7741184. 6: Tong Z, Narayanan R, Atsriku C, Nissel J, Li Y, Liu H, Wang X, Surapaneni S. Assessment of drug-drug interaction potential and PBPK modeling of CC-223, a potent inhibitor of the mammalian target of rapamycin kinase. Xenobiotica. 2019 Jan;49(1):54-70. doi: 10.1080/00498254.2018.1424377. Epub 2018 Jan 17. PMID: 29297772. 7: Tong Z, Atsriku C, Yerramilli U, Wang X, Nissel J, Li Y, Surapaneni S. Absorption, distribution, metabolism, and excretion of mTOR kinase inhibitor CC-223 in rats, dogs, and humans. Xenobiotica. 2019 Jan;49(1):43-53. doi: 10.1080/00498254.2017.1413718. Epub 2017 Dec 19. PMID: 29206565. 8: Mortensen DS, Perrin-Ninkovic SM, Shevlin G, Zhao J, Packard G, Bahmanyar S, Correa M, Elsner J, Harris R, Lee BG, Papa P, Parnes JS, Riggs JR, Sapienza J, Tehrani L, Whitefield B, Apuy J, Bisonette RR, Gamez JC, Hickman M, Khambatta G, Leisten J, Peng SX, Richardson SJ, Cathers BE, Canan SS, Moghaddam MF, Raymon HK, Worland P, Narla RK, Fultz KE, Sankar S. Discovery of mammalian target of rapamycin (mTOR) kinase inhibitor CC-223. J Med Chem. 2015 Jul 9;58(13):5323-33. doi: 10.1021/acs.jmedchem.5b00626. Epub 2015 Jun 26. PMID: 26083478. 9: Bendell JC, Kelley RK, Shih KC, Grabowsky JA, Bergsland E, Jones S, Martin T, Infante JR, Mischel PS, Matsutani T, Xu S, Wong L, Liu Y, Wu X, Mortensen DS, Chopra R, Hege K, Munster PN. A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma. Cancer. 2015 Oct 1;121(19):3481-90. doi: 10.1002/cncr.29422. Epub 2015 Jul 15. PMID: 26177599; PMCID: PMC4832308. 10: Wolin E, Mita A, Mahipal A, Meyer T, Bendell J, Nemunaitis J, Munster PN, Paz-Ares L, Filvaroff EH, Li S, Hege K, de Haan H, Mita M. A phase 2 study of an oral mTORC1/mTORC2 kinase inhibitor (CC-223) for non-pancreatic neuroendocrine tumors with or without carcinoid symptoms. PLoS One. 2019 Sep 17;14(9):e0221994. doi: 10.1371/journal.pone.0221994. PMID: 31527867; PMCID: PMC6748410. 11: Ashworth RE, Wu J. Mammalian target of rapamycin inhibition in hepatocellular carcinoma. World J Hepatol. 2014 Nov 27;6(11):776-82. doi: 10.4254/wjh.v6.i11.776. PMID: 25429315; PMCID: PMC4243151. 12: Orr-Asman MA, Chu Z, Jiang M, Worley M, LaSance K, Koch SE, Carreira VS, Dahche HM, Plas DR, Komurov K, Qi X, Mercer CA, Anthony LB, Rubinstein J, Thomas HE. mTOR Kinase Inhibition Effectively Decreases Progression of a Subset of Neuroendocrine Tumors that Progress on Rapalog Therapy and Delays Cardiac Impairment. Mol Cancer Ther. 2017 Nov;16(11):2432-2441. doi: 10.1158/1535-7163.MCT-17-0058. Epub 2017 Sep 1. PMID: 28864682. 13: Peiter GC, de Souza CBT, de Oliveira LM, Pagliarin LG, Dos Anjos VNF, da Silva FAF, de Melo FF, Teixeira KN. COVID-19 liver and gastroenterology findings: An in silico analysis of SARS-CoV-2 interactions with liver molecules. World J Hepatol. 2022 Jun 27;14(6):1131-1141. doi: 10.4254/wjh.v14.i6.1131. PMID: 35978663; PMCID: PMC9258260.

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