SBI0206965 | CAS#1884220-36-3 | Autophagy Kinase ULK1 Inhibitor

MedKoo Cat#: 407159 | Name: SBI0206965

Description:

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

SBI0206965 is a potent and selective autophagy Kinase ULK1 Inhibitor. Many tumors become addicted to autophagy for survival, suggesting inhibition of autophagy as a potential broadly applicable cancer therapy. SBI0206965 is a highly selective ULK1 kinase inhibitor in vitro and suppressed ULK1-mediated phosphorylation events in cells, regulating autophagy and cell survival. SBI0206965 greatly synergized with mechanistic target of rapamycin (mTOR) inhibitors to kill tumor cells, providing a strong rationale for their combined use in the clinic.

Chemical Structure

SBI0206965

CAS#1884220-36-3

Theoretical Analysis

MedKoo Cat#: 407159

Name: SBI0206965

CAS#: 1884220-36-3

Chemical Formula: C21H21BrN4O5

Exact Mass: 488.0695

Molecular Weight: 489.33

Elemental Analysis: C, 51.55; H, 4.33; Br, 16.33; N, 11.45; O, 16.35

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 225.00	Ready to ship
50mg	USD 385.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,150.00	Ready to ship
500mg	USD 2,450.00	Ready to ship
1g	USD 3,850.00	Ready to ship
2g	USD 6,450.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

SBI0206965; SBI-0206965; SBI 0206965.

IUPAC/Chemical Name

2-((5-bromo-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzamide

InChi Key

NEXGBSJERNQRSV-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H21BrN4O5/c1-23-19(27)13-7-5-6-8-15(13)31-20-14(22)11-24-21(26-20)25-12-9-16(28-2)18(30-4)17(10-12)29-3/h5-11H,1-4H3,(H,23,27)(H,24,25,26)

SMILES Code

O=C(NC)C1=CC=CC=C1OC2=NC(NC3=CC(OC)=C(OC)C(OC)=C3)=NC=C2Br

Appearance

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#SSC60107

View CoA: current batch, Lot#CRB50925

QC Data

View QC data: current batch, Lot#CRB50925

View QC data: current batch, Lot#SSC60107

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SBI0206965 is a cell permeable autophagy kinase ULK1 inhibitor with IC50s of 108 nM for ULK1 kinase and 711 nM for the highly related kinase ULK2.

In vitro activity:

SBI0206965 might offer a novel therapeutic approach for neuroblastoma treatment. SBI0206965 significantly reduced the growth of neuroblastoma cell lines, promoting apoptosis. SBI-0206965 treatment sensitized neuroblastoma cells to TRAIL therapy but did not enhance sensitivity to mTOR or topoisomerase inhibitors. Reference: Mol Cancer Ther. 2018 Nov; 17(11): 2365–2376. https://pubmed.ncbi.nlm.nih.gov/30166400/

In vivo activity:

SBI0206965 protected against acute axonal degeneration after rat optic nerve crush; SBI0206965 treatment enhanced mTOR activation. Reference: Cell Death Differ. 2020 Oct; 27(10): 2810–2827. https://pubmed.ncbi.nlm.nih.gov/32341448/

	Solvent	mg/mL	mM
Solubility
	DMSO	75.7	154.64
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.02
	DMF	30.0	61.31
	Ethanol	10.5	21.46

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 489.33 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. Ahwazi D, Neopane K, Markby GR, Kopietz F, Ovens AJ, Dall M, Hassing AS, Gräsle P, Alshuweishi Y, Treebak JT, Salt IP, Göransson O, Zeqiraj E, Scott JW, Sakamoto K. Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965. Biochem J. 2021 Aug 13;478(15):2977-2997. doi: 10.1042/BCJ20210284. PMID: 34259310; PMCID: PMC8370752. 2. Dower CM, Bhat N, Gebru MT, Chen L, Wills CA, Miller BA, Wang HG. Targeted Inhibition of ULK1 Promotes Apoptosis and Suppresses Tumor Growth and Metastasis in Neuroblastoma. Mol Cancer Ther. 2018 Nov;17(11):2365-2376. doi: 10.1158/1535-7163.MCT-18-0176. Epub 2018 Aug 30. PMID: 30166400; PMCID: PMC6215526. 3. Desai JM, Karve AS, Gudelsky GA, Gawali MV, Seibel W, Sallans L, DasGupta B, Desai PB. Brain pharmacokinetics and metabolism of the AMP-activated protein kinase selective inhibitor SBI-0206965, an investigational agent for the treatment of glioblastoma. Invest New Drugs. 2022 Oct;40(5):944-952. doi: 10.1007/s10637-022-01278-8. Epub 2022 Jul 8. PMID: 35802287; PMCID: PMC10154080. 4. Vahsen BF, Ribas VT, Sundermeyer J, Boecker A, Dambeck V, Lenz C, Shomroni O, Caldi Gomes L, Tatenhorst L, Barski E, Roser AE, Michel U, Urlaub H, Salinas G, Bähr M, Koch JC, Lingor P. Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing. Cell Death Differ. 2020 Oct;27(10):2810-2827. doi: 10.1038/s41418-020-0543-y. Epub 2020 Apr 27. PMID: 32341448; PMCID: PMC7493890.

In vitro protocol:

In vivo protocol:

1. Desai JM, Karve AS, Gudelsky GA, Gawali MV, Seibel W, Sallans L, DasGupta B, Desai PB. Brain pharmacokinetics and metabolism of the AMP-activated protein kinase selective inhibitor SBI-0206965, an investigational agent for the treatment of glioblastoma. Invest New Drugs. 2022 Oct;40(5):944-952. doi: 10.1007/s10637-022-01278-8. Epub 2022 Jul 8. PMID: 35802287; PMCID: PMC10154080. 2. Vahsen BF, Ribas VT, Sundermeyer J, Boecker A, Dambeck V, Lenz C, Shomroni O, Caldi Gomes L, Tatenhorst L, Barski E, Roser AE, Michel U, Urlaub H, Salinas G, Bähr M, Koch JC, Lingor P. Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing. Cell Death Differ. 2020 Oct;27(10):2810-2827. doi: 10.1038/s41418-020-0543-y. Epub 2020 Apr 27. PMID: 32341448; PMCID: PMC7493890.

1: Carty JS, Bessho R, Zuchowski Y, Trapani JB, Davidoff O, Kobayashi H, Roland JT, Watts JA, Terker AS, Bock F, Arroyo JP, Haase VH. Disruption of mitochondrial electron transport impairs urinary concentration via AMPK- dependent suppression of aquaporin 2. JCI Insight. 2024 Nov 22;9(22):e182087. doi: 10.1172/jci.insight.182087. PMID: 39361429; PMCID: PMC11601893. 2: Gu H, Qiu H, Yang H, Deng Z, Zhang S, Du L, He F. PRRSV utilizes MALT1-regulated autophagy flux to switch virus spread and reserve. Autophagy. 2024 Dec;20(12):2697-2718. doi: 10.1080/15548627.2024.2386195. Epub 2024 Aug 6. PMID: 39081059; PMCID: PMC11587858. 3: Dixon S, Tran A, Schrier MS, Dong J, Deth RC, Castejon A, Trivedi MS. Metformin-induced oxidative stress inhibits LNCaP prostate cancer cell survival. Mol Biol Rep. 2024 Jun 12;51(1):729. doi: 10.1007/s11033-024-09662-8. PMID: 38862809. 4: Zhao J, Yang T, Yi J, Hu H, Lai Q, Nie L, Liu M, Chu C, Yang J. AP39 through AMPK-ULK1-FUNDC1 pathway regulates mitophagy, inhibits pyroptosis, and improves doxorubicin-induced myocardial fibrosis. iScience. 2024 Feb 23;27(4):109321. doi: 10.1016/j.isci.2024.109321. PMID: 38558936; PMCID: PMC10981016. 5: Hawley SA, Russell FM, Ross FA, Hardie DG. BAY-3827 and SBI-0206965: Potent AMPK Inhibitors That Paradoxically Increase Thr172 Phosphorylation. Int J Mol Sci. 2023 Dec 29;25(1):453. doi: 10.3390/ijms25010453. PMID: 38203624; PMCID: PMC10778976. 6: Xiong Y, Cui MY, Li ZL, Fu YQ, Zheng Y, Yu Y, Zhang C, Huang XY, Chen BH. ULK1 confers neuroprotection by regulating microglial/macrophages activation after ischemic stroke. Int Immunopharmacol. 2024 Jan 25;127:111379. doi: 10.1016/j.intimp.2023.111379. Epub 2023 Dec 22. PMID: 38141409. 7: Kim HG, Ro MH, Lee M. Atg5 knockout induces alternative autophagy via the downregulation of Akt expression. Toxicol Res. 2023 Jun 5;39(4):637-647. doi: 10.1007/s43188-023-00191-3. PMID: 37779593; PMCID: PMC10541375. 8: Aleksandrova KV, Suvorova II. Evaluation of the Effectiveness of Various Autophagy Inhibitors in A549 Cancer Stem Cells. Acta Naturae. 2023 Jan- Mar;15(1):19-25. doi: 10.32607/actanaturae.11891. PMID: 37153502; PMCID: PMC10154774. 9: Chernyavskij DA, Pletjushkina OY, Kashtanova AV, Galkin II, Karpukhina A, Chernyak BV, Vassetzky YS, Popova EN. Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis. Antioxidants (Basel). 2023 Mar 1;12(3):602. doi: 10.3390/antiox12030602. PMID: 36978858; PMCID: PMC10044935. 10: Chou SH, Wan TW, Shiau CW, Chen LH, Lin HC, Chiu HC. Repurposing the tyrosine kinase inhibitor nilotinib for use against intracellular multidrug- resistant Salmonella Typhimurium. J Microbiol Immunol Infect. 2023 Jun;56(3):490-498. doi: 10.1016/j.jmii.2023.01.005. Epub 2023 Jan 17. PMID: 36702646. 11: Deng L, Jiang L, Wei N, Zhang J, Wu X. Anesthetic sevoflurane simultaneously regulates autophagic flux and pyroptotic cell death-associated cellular inflammation in the hypoxic/re-oxygenated cardiomyocytes: Identification of sevoflurane as putative drug for the treatment of myocardial ischemia- reperfusion injury. Eur J Pharmacol. 2022 Dec 5;936:175363. doi: 10.1016/j.ejphar.2022.175363. Epub 2022 Nov 4. PMID: 36343694. 12: Wang J, Kan X, Li X, Sun J, Xu X. Porcine epidemic diarrhoea virus (PEDV) infection activates AMPK and JNK through TAK1 to induce autophagy and enhance virus replication. Virulence. 2022 Dec;13(1):1697-1712. doi: 10.1080/21505594.2022.2127192. PMID: 36168145; PMCID: PMC9543055. 13: Desai JM, Karve AS, Gudelsky GA, Gawali MV, Seibel W, Sallans L, DasGupta B, Desai PB. Brain pharmacokinetics and metabolism of the AMP-activated protein kinase selective inhibitor SBI-0206965, an investigational agent for the treatment of glioblastoma. Invest New Drugs. 2022 Oct;40(5):944-952. doi: 10.1007/s10637-022-01278-8. Epub 2022 Jul 8. PMID: 35802287; PMCID: PMC10154080. 14: Wei B, Lu F, Kong Q, Huang Y, Huang K, Wu W. Trehalose induces B cell autophagy to alleviate myocardial injury via the AMPK/ULK1 signalling pathway in acute viral myocarditis induced by Coxsackie virus B3. Int J Biochem Cell Biol. 2022 May;146:106208. doi: 10.1016/j.biocel.2022.106208. Epub 2022 Apr 4. PMID: 35381374. 15: Yang M, Fu JD, Zou J, Sridharan D, Zhao MT, Singh H, Krigman J, Khan M, Xin G, Sun N. Assessment of mitophagy in human iPSC-derived cardiomyocytes. Autophagy. 2022 Oct;18(10):2481-2494. doi: 10.1080/15548627.2022.2037920. Epub 2022 Feb 27. PMID: 35220905; PMCID: PMC9542630. 16: Cruz AM, Partridge KM, Malekizadeh Y, Vlachaki Walker JM, Weightman Potter PG, Pye KR, Shaw SJ, Ellacott KLJ, Beall C. Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats. Front Endocrinol (Lausanne). 2021 Dec 17;12:697445. doi: 10.3389/fendo.2021.697445. PMID: 34975743; PMCID: PMC8718766. 17: Zhang S, Xie Y, Yan F, Zhang Y, Yang Z, Chen Z, Zhao Y, Huang Z, Cai L, Deng Z. Negative pressure wound therapy improves bone regeneration by promoting osteogenic differentiation via the AMPK-ULK1-autophagy axis. Autophagy. 2022 Sep;18(9):2229-2245. doi: 10.1080/15548627.2021.2016231. Epub 2021 Dec 29. PMID: 34964701; PMCID: PMC9466622. 18: Zhang Y, Yan M, Kuang S, Lou Y, Wu S, Li Y, Wang Z, Mao H. Bisphenol A induces apoptosis and autophagy in murine osteocytes MLO-Y4: Involvement of ROS- mediated mTOR/ULK1 pathway. Ecotoxicol Environ Saf. 2022 Jan 15;230:113119. doi: 10.1016/j.ecoenv.2021.113119. Epub 2021 Dec 23. PMID: 34954677. 19: Han Y, Xiong S, Zhao H, Yang S, Yang M, Zhu X, Jiang N, Xiong X, Gao P, Wei L, Xiao Y, Sun L. Lipophagy deficiency exacerbates ectopic lipid accumulation and tubular cells injury in diabetic nephropathy. Cell Death Dis. 2021 Oct 30;12(11):1031. doi: 10.1038/s41419-021-04326-y. PMID: 34718329; PMCID: PMC8557213. 20: Qiu X, Zheng L, Liu X, Hong D, He M, Tang Z, Tian C, Tan G, Hwang S, Shi Z, Wang L. ULK1 Inhibition as a Targeted Therapeutic Strategy for Psoriasis by Regulating Keratinocytes and Their Crosstalk With Neutrophils. Front Immunol. 2021 Aug 4;12:714274. doi: 10.3389/fimmu.2021.714274. PMID: 34421918; PMCID: PMC8371267.