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MedKoo Cat#: 565267 | Name: MDL-800
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Description:

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

MDL-800 is an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer. MDL-800 increased SIRT6 deacetylase activity with an EC50 value of 11.0 ± 0.3 μM; MDL-800 (10-50 μM) induced dose-dependent deacetylation of histone H3 in 12 NSCLC cell lines. Treatment with MDL-800 dose dependently inhibited the proliferation of 12 NSCLC cell lines with IC50 values ranging from 21.5 to 34.5 μM. The antiproliferation effect of MDL-800 was significantly diminished by SIRT6 knockout. Treatment with MDL-800 induced remarkable cell cycle arrest at the G0/G1 phase in NSCLC HCC827 and PC9 cells. Furthermore, MDL-800 (25, 50 μM) enhanced the antiproliferation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in osimertinib-resistant HCC827 and PC9 cells as well as in patient-derived primary tumor cells, and suppressed mitogen-activated protein kinase (MAPK) pathway.

Chemical Structure

MDL-800
MDL-800
CAS#2275619-53-7

Theoretical Analysis

MedKoo Cat#: 565267

Name: MDL-800

CAS#: 2275619-53-7

Chemical Formula: C21H16BrCl2FN2O6S2

Exact Mass: 623.8994

Molecular Weight: 626.29

Elemental Analysis: C, 40.27; H, 2.58; Br, 12.76; Cl, 11.32; F, 3.03; N, 4.47; O, 15.33; S, 10.24

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 750.00 Ready to ship
500mg USD 1,650.00 Ready to Ship
1g USD 2,950.00 Ready to Ship
2g USD 5,250.00 Ready to Ship
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No Data
Synonym
MDL800; MDL 800; MDL-800
IUPAC/Chemical Name
Methyl 2-(N-(5-bromo-4-fluoro-2-methylphenyl)sulfamoyl)-5-((3,5-dichlorophenyl)sulfonamido)benzoate
InChi Key
FKFQBYBODAKGOA-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H16BrCl2FN2O6S2/c1-11-5-18(25)17(22)10-19(11)27-35(31,32)20-4-3-14(9-16(20)21(28)33-2)26-34(29,30)15-7-12(23)6-13(24)8-15/h3-10,26-27H,1-2H3
SMILES Code
O=C(OC)C1=CC(NS(=O)(C2=CC(Cl)=CC(Cl)=C2)=O)=CC=C1S(=O)(NC3=CC(Br)=C(F)C=C3C)=O
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
Shelf Life
>3 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
Sirtuin 6 (SIRT6), a member of the sirtuin family, is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that is involved in various physiological and pathological processes. SIRT6 is generally downregulated and linked to tumorigenesis in non-small cell lung carcinoma (NSCLC), thus regarded as a promising therapeutic target of NSCLC. In HCC827 cell-derived xenograft nude mice, intraperitoneal administration of MDL-800 (80 mg · kg-1 · d-1, for 14 days) markedly suppressed the tumor growth, accompanied by enhanced SIRT6-dependent histone H3 deacetylation and decreased p-MEK and p-ERK in tumor tissues. MDL-800 improves genomic stability and pluripotency of old murine-derived iPS cells
Biological target:
MDL-800 is an allosteric and selective SIRT6 activator that increases SIRT6 deacetylation activity with an EC50 of 10.3 µM.
In vitro activity:
MDL‐800 (Figure1a) is a selective allosteric activator of SIRT6. It stimulates SIRT6 catalytic activity and promotes the binding affinities of substrate to SIRT6. It was therefore tested whether MDL‐800 treatment improved the quality of old murine (2‐year‐old)derived iPSCs. It was first validated that MDL‐800 enhances the enzymatic activity of mouse SIRT6. The iPSCs (induced pluripotent stem cells) derived from the old mice with MDL‐800 were pretreated at concentrations of 5 μM and 20 μM for 24 hr, and then analyzed the level of a SIRT6 substrate H3K56Ac. It was found that, consistent with previous reports on human SIRT6, treating the mouse iPSCs with MDL‐800 at 20 μM promoted the deacetylation of H3K56Ac (Figure1b), and prolonging the incubation time to 48 hr led to a further reduction in acetylation level of H3K56Ac (Figure1c). These data indicate that MDL‐800 might also directly activate the catalytic activity of mouse SIRT6. To further demonstrate that MDL‐800 affects the acetylation level of H3K56Ac through monitoring mouse SIRT6 activity, iPSCs derived from Sirt6 +/+ mouse embryonic fibroblasts (MEFs) or Sirt6 −/− MEFs were treated with MDL‐800. It was found that Sirt6 deficiency abrogated the MDL‐800 mediated promotion of H3K56Ac deacetylation (Figure S1a,b). Taken together, the results indicate that MDL‐800 specifically activates SIRT6 enzymatic activity in mouse iPSCs. Reference: Aging Cell. 2020 Aug; 19(8): e13185. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431819/
In vivo activity:
The pluripotency and in vivo differentiation potential of mouse iPSCs were evaluated by chimera experiments. Old C57BL/6 murinederived iPSCs were first infected with lentivirus bearing vectors encoding GFP for labeling, and the GFP+ cells were sorted by FACS. GFP+ mouse iPSCs were pretreated with MDL‐800 before microinjection into blastocysts. Then, the embryos were transplanted into the uteruses of pseudo‐pregnant ICR mice. Strikingly, it was found that embryos generated from mouse iPSCs treated with MDL‐800 showed a stronger green fluorescence, indicating a higher capacity to differentiate into three lineages in chimeric mice (Figure2b). In addition, the skins of embryos were dissociated into single cells and assessed by FACS for quantitative analysis. The result clearly showed that the percentage of GFP+ cells were approximately 3‐fold higher in MDL‐800 treated group than in the control group (Figure2c), indicating an improvement in in vivo differentiation of the same cell line upon MDL‐800 treatment. Further evidence from agouti coat color of the adult mice gave a similar result. There was a remarkable increase in the percentage of mice with a chimeric black coat color in the MDL‐800 treated group as compared to control group (Figure 2d,e). Reference: Aging Cell. 2020 Aug; 19(8): e13185. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431819/
Solvent mg/mL mM
Solubility
DMSO 125.0 199.58
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 626.29 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. Zhang J, Li Y, Liu Q, Huang Y, Li R, Wu T, Zhang Z, Zhou J, Huang H, Tang Q, Huang C, Zhao Y, Zhang G, Jiang W, Mo L, Zhang J, Xie W, He J. Sirt6 Alleviated Liver Fibrosis by Deacetylating Conserved Lysine 54 on Smad2 in Hepatic Stellate Cells. Hepatology. 2021 Mar;73(3):1140-1157. doi: 10.1002/hep.31418. Epub 2020 Nov 10. PMID: 32535965; PMCID: PMC8048913.
In vitro protocol:
1. Zhang J, Li Y, Liu Q, Huang Y, Li R, Wu T, Zhang Z, Zhou J, Huang H, Tang Q, Huang C, Zhao Y, Zhang G, Jiang W, Mo L, Zhang J, Xie W, He J. Sirt6 Alleviated Liver Fibrosis by Deacetylating Conserved Lysine 54 on Smad2 in Hepatic Stellate Cells. Hepatology. 2021 Mar;73(3):1140-1157. doi: 10.1002/hep.31418. Epub 2020 Nov 10. PMID: 32535965; PMCID: PMC8048913.
In vivo protocol:
1. Zhang J, Li Y, Liu Q, Huang Y, Li R, Wu T, Zhang Z, Zhou J, Huang H, Tang Q, Huang C, Zhao Y, Zhang G, Jiang W, Mo L, Zhang J, Xie W, He J. Sirt6 Alleviated Liver Fibrosis by Deacetylating Conserved Lysine 54 on Smad2 in Hepatic Stellate Cells. Hepatology. 2021 Mar;73(3):1140-1157. doi: 10.1002/hep.31418. Epub 2020 Nov 10. PMID: 32535965; PMCID: PMC8048913.
1: Copp ME, Shine J, Brown HL, Nimmala KR, Hansen OB, Chubinskaya S, Collins JA, Loeser RF, Diekman BO. Sirtuin 6 activation rescues the age-related decline in DNA damage repair in primary human chondrocytes. Aging (Albany NY). 2023 Dec 9;15(23):13628-13645. doi: 10.18632/aging.205394. Epub 2023 Dec 9. PMID: 38078876; PMCID: PMC10756124. 2: Wu S, Zhang J, Peng C, Ma Y, Tian X. SIRT6 mediated histone H3K9ac deacetylation involves myocardial remodelling through regulating myocardial energy metabolism in TAC mice. J Cell Mol Med. 2023 Nov;27(22):3451-3464. doi: 10.1111/jcmm.17915. Epub 2023 Aug 21. PMID: 37603612; PMCID: PMC10660608. 3: Collins JA, Kim CJ, Coleman A, Little A, Perez MM, Clarke EJ, Diekman B, Peffers MJ, Chubinskaya S, Tomlinson RE, Freeman TA, Loeser RF. Cartilage- specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice. Ann Rheum Dis. 2023 Nov;82(11):1464-1473. doi: 10.1136/ard-2023-224385. Epub 2023 Aug 7. PMID: 37550003; PMCID: PMC10579179. 4: Abbotto E, Miro C, Piacente F, Salis A, Murolo M, Nappi A, Millo E, Russo E, Cichero E, Sturla L, Del Rio A, De Flora A, Nencioni A, Dentice M, Bruzzone S. SIRT6 pharmacological inhibition delays skin cancer progression in the squamous cell carcinoma. Biomed Pharmacother. 2023 Oct;166:115326. doi: 10.1016/j.biopha.2023.115326. Epub 2023 Aug 21. PMID: 37611438. 5: Shen C, Jiang Y, Lin J, He Y, Liu Y, Fang D. SIRT6 reduces the symptoms of premature ovarian failure and alleviates oxidative stress and apoptosis in granulosa cells by degrading p66SHC via H3K9AC. Gynecol Endocrinol. 2023 Aug 17;39(1):2250003. doi: 10.1080/09513590.2023.2250003. PMID: 37634527. 6: Copp ME, Shine J, Brown HL, Nimmala KR, Chubinskaya S, Collins JA, Loeser RF, Diekman BO. SIRT6 activation rescues the age-related decline in DNA damage repair in primary human chondrocytes. bioRxiv [Preprint]. 2023 Feb 28:2023.02.27.530205. doi: 10.1101/2023.02.27.530205. Update in: Aging (Albany NY). 2023 Dec 9;15(23):13628-13645. PMID: 36909504; PMCID: PMC10002640. 7: Jin R, Niu C, Wu F, Zhou S, Han T, Zhang Z, Li E, Zhang X, Xu S, Wang J, Tian S, Chen W, Ye Q, Cao C, Cheng L. DNA damage contributes to age-associated differences in SARS-CoV-2 infection. Aging Cell. 2022 Dec;21(12):e13729. doi: 10.1111/acel.13729. Epub 2022 Oct 18. PMID: 36254583; PMCID: PMC9741512. 8: Wu X, Liu H, Brooks A, Xu S, Luo J, Steiner R, Mickelsen DM, Moravec CS, Jeffrey AD, Small EM, Jin ZG. SIRT6 Mitigates Heart Failure With Preserved Ejection Fraction in Diabetes. Circ Res. 2022 Nov 11;131(11):926-943. doi: 10.1161/CIRCRESAHA.121.318988. Epub 2022 Oct 24. Erratum in: Circ Res. 2023 Jul 21;133(3):e48. PMID: 36278398; PMCID: PMC9669223. 9: Wang Z, Wu Q, Wang H, Gao Y, Nie K, Tang Y, Su H, Hu M, Gong J, Fang K, Dong H. Diosgenin protects against podocyte injury in early phase of diabetic nephropathy through regulating SIRT6. Phytomedicine. 2022 Sep;104:154276. doi: 10.1016/j.phymed.2022.154276. Epub 2022 Jun 13. PMID: 35728388. 10: Ren SC, Chen X, Gong H, Wang H, Wu C, Li PH, Chen XF, Qu JH, Tang X. SIRT6 in Vascular Diseases, from Bench to Bedside. Aging Dis. 2022 Jul 11;13(4):1015-1029. doi: 10.14336/AD.2021.1204. PMID: 35855341; PMCID: PMC9286919. 11: Jin J, Li W, Wang T, Park BH, Park SK, Kang KP. Loss of Proximal Tubular Sirtuin 6 Aggravates Unilateral Ureteral Obstruction-Induced Tubulointerstitial Inflammation and Fibrosis by Regulation of β-Catenin Acetylation. Cells. 2022 Apr 27;11(9):1477. doi: 10.3390/cells11091477. PMID: 35563783; PMCID: PMC9100256. 12: Jiang X, Yao Z, Wang K, Lou L, Xue K, Chen J, Zhang G, Zhang Y, Du J, Lin C, Xiao J. MDL-800, the SIRT6 Activator, Suppresses Inflammation via the NF-κB Pathway and Promotes Angiogenesis to Accelerate Cutaneous Wound Healing in Mice. Oxid Med Cell Longev. 2022 Apr 27;2022:1619651. doi: 10.1155/2022/1619651. PMID: 35528512; PMCID: PMC9068290. 13: Zhang J, Li Y, Liu Q, Huang Y, Li R, Wu T, Zhang Z, Zhou J, Huang H, Tang Q, Huang C, Zhao Y, Zhang G, Jiang W, Mo L, Zhang J, Xie W, He J. Sirt6 Alleviated Liver Fibrosis by Deacetylating Conserved Lysine 54 on Smad2 in Hepatic Stellate Cells. Hepatology. 2021 Mar;73(3):1140-1157. doi: 10.1002/hep.31418. Epub 2020 Nov 10. PMID: 32535965; PMCID: PMC8048913. 14: Shang JL, Ning SB, Chen YY, Chen TX, Zhang J. MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer. Acta Pharmacol Sin. 2021 Jan;42(1):120-131. doi: 10.1038/s41401-020-0442-2. Epub 2020 Jun 15. PMID: 32541922; PMCID: PMC7921659. 15: Chen Y, Chen J, Sun X, Yu J, Qian Z, Wu L, Xu X, Wan X, Jiang Y, Zhang J, Gao S, Mao Z. The SIRT6 activator MDL-800 improves genomic stability and pluripotency of old murine-derived iPS cells. Aging Cell. 2020 Aug;19(8):e13185. doi: 10.1111/acel.13185. Epub 2020 Jul 21. PMID: 33089974; PMCID: PMC7431819. 16: Huang Z, Zhao J, Deng W, Chen Y, Shang J, Song K, Zhang L, Wang C, Lu S, Yang X, He B, Min J, Hu H, Tan M, Xu J, Zhang Q, Zhong J, Sun X, Mao Z, Lin H, Xiao M, Chin YE, Jiang H, Xu Y, Chen G, Zhang J. Identification of a cellularly active SIRT6 allosteric activator. Nat Chem Biol. 2018 Dec;14(12):1118-1126. doi: 10.1038/s41589-018-0150-0. Epub 2018 Oct 29. PMID: 30374165.
Xia F, Shi S, Palacios E, Liu W, Buscho SE, Li J, Huang S, Vizzeri G, Dong XC, Motamedi M, Zhang W, Liu H. Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma. Mol Ther. 2024 Apr 24:S1525-0016(24)00253-3. doi: 10.1016/j.ymthe.2024.04.030. Epub ahead of print. PMID: 38659223.