Rebastinib free base | CAS#1020172-07-9 | Kinase inhibitor

MedKoo Cat#: 200851 | Name: Rebastinib free base

Description:

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

Rebastinib (DCC-2036) is a potent, orally bioavailable tyrosine kinase inhibitor that primarily targets the ABL1 kinase, including the T315I gatekeeper mutation associated with resistance to first- and second-generation BCR-ABL inhibitors. It exhibits nanomolar potency, with reported IC₅₀ values of approximately 0.8 nM against wild-type BCR-ABL and 4 nM against the T315I mutant in enzymatic assays. Rebastinib also inhibits other kinases such as Tie2 (TEK), with an IC₅₀ of ~1.2 nM, implicating additional anti-angiogenic and anti-metastatic potential. In cellular assays, rebastinib demonstrates sub-nanomolar to low nanomolar activity against BCR-ABL–expressing leukemia cells, including those harboring the T315I mutation, with corresponding inhibition of downstream signaling (e.g., STAT5 phosphorylation). Preclinical studies show significant tumor regression and prolonged survival in mouse xenograft models of chronic myeloid leukemia (CML) and solid tumors.

Chemical Structure

Rebastinib free base

CAS#1020172-07-9 (free base)

Theoretical Analysis

MedKoo Cat#: 200851

Name: Rebastinib free base

CAS#: 1020172-07-9 (free base)

Chemical Formula: C30H28FN7O3

Exact Mass: 553.2238

Molecular Weight: 553.59

Elemental Analysis: C, 65.09; H, 5.10; F, 3.43; N, 17.71; O, 8.67

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 425.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,050.00	Ready to ship

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Related CAS #

1020172-07-9 (free base) 1033893-29-6 (tosylate)

Synonym

DCC2036; DCC-2036; DCC 2036; Rebastinib.

IUPAC/Chemical Name

N-[3-tert-Butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]-N'-[2-fluoro-4-[(2-(methylcarbamoyl)pyridin-4-yl)oxy]phenyl]urea

InChi Key

WVXNSAVVKYZVOE-UHFFFAOYSA-N

InChi Code

InChI=1S/C30H28FN7O3/c1-30(2,3)26-17-27(38(37-26)19-7-9-23-18(14-19)6-5-12-33-23)36-29(40)35-24-10-8-20(15-22(24)31)41-21-11-13-34-25(16-21)28(39)32-4/h5-17H,1-4H3,(H,32,39)(H2,35,36,40)

SMILES Code

O=C(NC1=CC=C(OC2=CC(C(NC)=O)=NC=C2)C=C1F)NC3=CC(C(C)(C)C)=NN3C4=CC=C5N=CC=CC5=C4

Appearance

White to off-white 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

DCC-2036 inhibits BCR-ABL kinase, an oncogenic fusion protein kinase resulting from chromosomal translocation (Philadelphia + chromosome). BCR-ABL is causative of myeloproliferative diseases, including chronic myelogenous leukemia (CML). In preclinical studies, DCC-2036 has demonstrated potent enzymatic and cellular inhibition of BCR-ABL, the T315I gatekeeper mutant, and other clinically relevant P-loop & Activation loop mutants. DCC-2036 is highly efficacious in animal models of human T315I CML. DCC-2036 is being developed as an orally administered treatment for CML. See Deciphera's webpage.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S7S11C15

QC Data

View QC data: current batch, Lot#S7S11C15

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Rebastinib is a Bcr-Abl inhibitor for Abl1WT and Abl1T315I with IC50s of 0.8 nM and 4 nM, respectively.

In vitro activity:

The effects of rebastinib on cell infiltration and, in particular, Tie2+ macrophage infiltration were evaluated. Rebastinib significantly decreased both total and Tie2+ macrophages (Figure 3A–C) but did not significantly affect lymphoid immune cell composition (Figure S8). There was a trend toward reduction of M2-polarized macrophages (Figure 3B) and the subset of M2 macrophages expressing Tie2 (Figure S8), however this reduction did not achieve significance. In a separate analysis, multichannel Immunofluorescence (IF) staining (Iba1 for macrophages, CD31 for endothelium and Tie2) was used to specifically distinguish the Tie2+ macrophage subpopulation (Figures 3D–E) and demonstrated that the Tie2+ macrophage subpopulation was significantly decreased in response to rebastinib treatment (Figures 3D–E and Figure S9A), confirming the reduction in the Tie2+ macrophage subpopulation in response to rebastinib (Figure 3C). Reference: Mol Cancer Ther. 2017 Nov;16(11):2486-2501. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669998/

In vivo activity:

To examine rebastinib inhibition of Tie2 signaling in vivo, an orthotopic mouse mammary cancer implant model in which the polyoma middle T antigen is under the control of the mouse mammary tumor virus long terminal repeat (MMTV-PyMT) was used. Rebastinib significantly reduced primary tumor growth by 75% and more importantly, when used in combination with paclitaxel, rebastinib had an additive effect in reducing tumor growth by 90% of control (Figure 2A). The data demonstrated that rebastinib treatment in PyMT (Polyoma Middle T) mammary tumors either daily, or through intermittent dosing alone or in combination with chemotherapy, reduces primary tumor volume and extends survival time. Reference: Mol Cancer Ther. 2017 Nov;16(11):2486-2501. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669998/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.0	54.20
	DMF	30.0	54.20
	Ethanol	1.0	1.80

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 553.59 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.

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. Harney AS, Karagiannis GS, Pignatelli J, Smith BD, Kadioglu E, Wise SC, Hood MM, Kaufman MD, Leary CB, Lu WP, Al-Ani G, Chen X, Entenberg D, Oktay MH, Wang Y, Chun L, De Palma M, Jones JG, Flynn DL, Condeelis JS. The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2Hi Macrophages in Breast Cancer and Pancreatic Neuroendocrine Tumors. Mol Cancer Ther. 2017 Nov;16(11):2486-2501. doi: 10.1158/1535-7163.MCT-17-0241. Epub 2017 Aug 24. PMID: 28838996; PMCID: PMC5669998.

In vitro protocol:

In vivo protocol:

1: Zaini A, Jawad HE, Al-Mudhafar DH, Hadi NR. Rebastinib attenuates liver injury following cecal ligation and puncture in male mice. J Med Life. 2023 Nov;16(11):1678-1684. doi: 10.25122/jml-2023-0089. PMID: 38406786; PMCID: PMC10893574. 2: Karagiannis GS, Pastoriza JM, Wang Y, Harney AS, Entenberg D, Pignatelli J, Sharma VP, Xue EA, Cheng E, D'Alfonso TM, Jones JG, Anampa J, Rohan TE, Sparano JA, Condeelis JS, Oktay MH. Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Sci Transl Med. 2017 Jul 5;9(397):eaan0026. doi: 10.1126/scitranslmed.aan0026. Erratum in: Sci Transl Med. 2017 Jul 19;9(399):eaao3817. doi: 10.1126/scitranslmed.aao3817. PMID: 28679654; PMCID: PMC5592784. 3: Li X, Li J, Xu L, Wei W, Cheng A, Zhang L, Zhang M, Wu G, Cai C. CDK16 promotes the progression and metastasis of triple-negative breast cancer by phosphorylating PRC1. J Exp Clin Cancer Res. 2022 Apr 21;41(1):149. doi: 10.1186/s13046-022-02362-w. PMID: 35449080; PMCID: PMC9027050. 4: Feng K, Jian C, Xiao H, Jiang H, Yang J, Yang M, Sun A, Song W, Chestkov AV, Vasilevich NI, Sun L. The Suppressive Effect of Rebastinib on Triple-negative Breast Cancer Tumors Involves Multiple Mechanisms of Action. Anticancer Res. 2023 Jun;43(6):2609-2624. doi: 10.21873/anticanres.16428. PMID: 37247937. 5: Triana P, Lopez-Gutierrez JC. Activity of a TIE2 inhibitor (rebastinib) in a patient with a life-threatening cervicofacial venous malformation. Pediatr Blood Cancer. 2023 Aug;70(8):e30404. doi: 10.1002/pbc.30404. Epub 2023 May 9. PMID: 37158500. 6: Harney AS, Karagiannis GS, Pignatelli J, Smith BD, Kadioglu E, Wise SC, Hood MM, Kaufman MD, Leary CB, Lu WP, Al-Ani G, Chen X, Entenberg D, Oktay MH, Wang Y, Chun L, De Palma M, Jones JG, Flynn DL, Condeelis JS. The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2Hi Macrophages in Breast Cancer and Pancreatic Neuroendocrine Tumors. Mol Cancer Ther. 2017 Nov;16(11):2486-2501. doi: 10.1158/1535-7163.MCT-17-0241. Epub 2017 Aug 24. PMID: 28838996; PMCID: PMC5669998. 7: Cortes J, Talpaz M, Smith HP, Snyder DS, Khoury J, Bhalla KN, Pinilla-Ibarz J, Larson R, Mitchell D, Wise SC, Rutkoski TJ, Smith BD, Flynn DL, Kantarjian HM, Rosen O, Van Etten RA. Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia. Haematologica. 2017 Mar;102(3):519-528. doi: 10.3324/haematol.2016.152710. Epub 2016 Dec 7. PMID: 27927766; PMCID: PMC5394958. 8: Cam M, Charan M, Welker AM, Dravid P, Studebaker AW, Leonard JR, Pierson CR, Nakano I, Beattie CE, Hwang EI, Kambhampati M, Nazarian J, Finlay JL, Cam H. ΔNp73/ETS2 complex drives glioblastoma pathogenesis- targeting downstream mediators by rebastinib prolongs survival in preclinical models of glioblastoma. Neuro Oncol. 2020 Mar 5;22(3):345-356. doi: 10.1093/neuonc/noz190. PMID: 31763674; PMCID: PMC7058445. 9: Chabner BA. Does Chemotherapy Induce Metastases? Oncologist. 2018 Mar;23(3):273-274. doi: 10.1634/theoncologist.2017-0648. PMID: 29523674; PMCID: PMC5905696. 10: Muskat A, Nawrocki S, Kost Y, Mattis D, Amin B, McLellan B. Verruca Vulgaris Eruption Arising in the Setting of a Tyrosine Kinase Inhibitor. Cureus. 2022 Jun 16;14(6):e26006. doi: 10.7759/cureus.26006. PMID: 35855241; PMCID: PMC9286299. 11: Koch PD, Ahmed MS, Kohler RH, Li R, Weissleder R. Imaging of Tie2 with a Fluorescently Labeled Small Molecule Affinity Ligand. ACS Chem Biol. 2020 Jan 17;15(1):151-157. doi: 10.1021/acschembio.9b00724. Epub 2019 Dec 13. PMID: 31809013; PMCID: PMC7808335. 12: Tasegian A, Singh F, Ganley IG, Reith AD, Alessi DR. Impact of Type II LRRK2 inhibitors on signaling and mitophagy. Biochem J. 2021 Oct 15;478(19):3555-3573. doi: 10.1042/BCJ20210375. PMID: 34515301; PMCID: PMC8589421. 13: Gavrilin MA, Prather ER, Vompe AD, McAndrew CC, Wewers MD. cAbl Kinase Regulates Inflammasome Activation and Pyroptosis via ASC Phosphorylation. J Immunol. 2021 Mar 15;206(6):1329-1336. doi: 10.4049/jimmunol.2000969. Epub 2021 Feb 10. PMID: 33568399; PMCID: PMC7946721. 14: Dixon-Clarke SE, Shehata SN, Krojer T, Sharpe TD, von Delft F, Sakamoto K, Bullock AN. Structure and inhibitor specificity of the PCTAIRE-family kinase CDK16. Biochem J. 2017 Feb 20;474(5):699-713. doi: 10.1042/BCJ20160941. PMID: 28057719; PMCID: PMC5317395. 15: Rossari F, Minutolo F, Orciuolo E. Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy. J Hematol Oncol. 2018 Jun 20;11(1):84. doi: 10.1186/s13045-018-0624-2. PMID: 29925402; PMCID: PMC6011351. 16: Marguier A, Laheurte C, Lecoester B, Malfroy M, Boullerot L, Renaudin A, Seffar E, Kumar A, Nardin C, Aubin F, Adotevi O. TIE-2 Signaling Activation by Angiopoietin 2 On Myeloid-Derived Suppressor Cells Promotes Melanoma-Specific T-cell Inhibition. Front Immunol. 2022 Jul 22;13:932298. doi: 10.3389/fimmu.2022.932298. PMID: 35935946; PMCID: PMC9353943. 17: Karagiannis GS, Bianchi A, Sanchez LR, Ambadipudi K, Cui MH, Anampa JM, Asiry S, Wang Y, Harney AS, Pastoriza JM, Lin Y, Chen X, Jones JG, Entenberg D, Haddad D, Hodges LJ, Duong TQ, Sparano JA, Oktay MH, Branch CA, Condeelis JS. Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy. NPJ Breast Cancer. 2022 Sep 2;8(1):101. doi: 10.1038/s41523-022-00463-5. PMID: 36056005; PMCID: PMC9440218. 18: Zhu H, Hixson P, Ma W, Sun J. Pharmacology of LRRK2 with type I and II kinase inhibitors revealed by cryo-EM. Cell Discov. 2024 Jan 23;10(1):10. doi: 10.1038/s41421-023-00639-8. Erratum in: Cell Discov. 2024 Feb 26;10(1):23. doi: 10.1038/s41421-024-00660-5. PMID: 38263358; PMCID: PMC10805800. 19: Sharda S, Sarmandal P, Cherukommu S, Dindhoria K, Yadav M, Bandaru S, Sharma A, Sakhi A, Vyas T, Hussain T, Nayarisseri A, Singh SK. A Virtual Screening Approach for the Identification of High Affinity Small Molecules Targeting BCR- ABL1 Inhibitors for the Treatment of Chronic Myeloid Leukemia. Curr Top Med Chem. 2017;17(26):2989-2996. doi: 10.2174/1568026617666170821124512. PMID: 28828991. 20: Weng JH, Ma W, Wu J, Sharma PK, Silletti S, McCammon JA, Taylor S. Capturing Differences in the Regulation of LRRK2 Dynamics and Conformational States by Small Molecule Kinase Inhibitors. ACS Chem Biol. 2023 Apr 21;18(4):810-821. doi: 10.1021/acschembio.2c00868. Epub 2023 Apr 12. PMID: 37043829; PMCID: PMC10127209.