Name: SD-36
Brand: BOC Sciences
Rating: 5 (1 reviews)

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Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Solid Powder

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

IUPACName

[[2-[[(5S,8S,10aR)-8-[[(2S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl]carbamoyl]-3-[8-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]oct-7-ynoyl]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-5-yl]carbamoyl]-1H-indol-5-yl]-difluoromethyl]phosphonic acid

Synonyms

Phosphonic acid, P-[[2-[[[(5S,8S,10aR)-8-[[[(1S)-4-amino-1-[[(diphenylmethyl)amino]carbonyl]-4-oxobutyl]amino]carbonyl]-3-[8-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1-oxo-1H-isoindol-4-yl]-1-oxo-7-octyn-1-yl]decahydro-6-oxopyrrolo[1,2-a][1,5]diazocin-5-yl]amino]carbonyl]-1H-indol-5-yl]difluoromethyl]-; ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-3-(8-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oct-7-ynoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid; P-[[2-[[[(5S,8S,10aR)-8-[[[(1S)-4-Amino-1-[[(diphenylmethyl)amino]carbonyl]-4-oxobutyl]amino]carbonyl]-3-[8-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1-oxo-1H-isoindol-4-yl]-1-oxo-7-octyn-1-yl]decahydro-6-oxopyrrolo[1,2-a][1,5]diazocin-5-yl]amino]carbonyl]-1H-indol-5-yl]difluoromethyl]phosphonic acid; SD 36; SD36

Density

1.50±0.1 g/cm3

InChI Key

JKCSCHXVWPSGBG-OPKPGBGESA-N

InChI

InChI=1S/C59H62F2N9O12P/c60-59(61,83(80,81)82)39-21-23-43-38(31-39)32-45(63-43)54(75)65-46-34-68(51(73)20-11-3-1-2-6-13-35-18-12-19-41-42(35)33-69(57(41)78)47-26-28-50(72)66-55(47)76)30-29-40-22-25-48(70(40)58(46)79)56(77)64-44(24-27-49(62)71)53(74)67-52(36-14-7-4-8-15-36)37-16-9-5-10-17-37/h4-5,7-10,12,14-19,21,23,31-32,40,44,46-48,52,63H,1-3,11,20,22,24-30,33-34H2,(H2,62,71)(H,64,77)(H,65,75)(H,67,74)(H,66,72,76)(H2,80,81,82)/t40-,44+,46+,47?,48+/m1/s1

SMILES

C1CC(N2C1CCN(CC(C2=O)NC(=O)C3=CC4=C(N3)C=CC(=C4)C(F)(F)P(=O)(O)O)C(=O)CCCCCC#CC5=C6CN(C(=O)C6=CC=C5)C7CCC(=O)NC7=O)C(=O)NC(CCC(=O)N)C(=O)NC(C8=CC=CC=C8)C9=CC=CC=C9

Mechanism

Target: Targets STAT3 transcription factor for experimental targeted protein degradation studies.

Binding Site: Binds the STAT3 SH2 phosphotyrosine-binding domain and cereblon thalidomide-binding pocket to support productive ternary complex formation.

Mechanism of Action: SD-36 is designed for use in PROTAC or targeted protein degradation experiments directed toward STAT3 transcription factor. The bifunctional molecule links a target-recognition element to cereblon, promoting proximity between the protein of interest and ubiquitination machinery. Productive ternary-complex formation can drive polyubiquitination and proteasome-dependent target depletion, allowing researchers to compare pharmacological inhibition with protein removal. It is suitable for evaluating degradation potency, kinetics, pathway selectivity, and downstream signaling consequences in engineered or disease-relevant cellular models.

Applications

• PROTAC-Mediated STAT3 Degradation: SD-36 is a potent PROTAC designed for the targeted degradation of STAT3, a transcription factor implicated in various cancers. By promoting the ubiquitination and subsequent proteasomal degradation of STAT3, SD-36 serves as a valuable tool in cancer research, enabling the exploration of STAT3's role in tumorigenesis and potential therapeutic interventions.

• Targeted Protein Degradation in Oncology: Utilizing SD-36 allows researchers to investigate the effects of selective STAT3 degradation on cancer cell survival and proliferation. This PROTAC facilitates studies on the modulation of oncogenic signaling pathways, offering insights into novel strategies for targeted cancer therapies.

• Mechanistic Studies of PROTAC Efficacy: SD-36 provides a model for studying the mechanistic aspects of PROTACs, including the recruitment of E3 ligases and the dynamics of protein ubiquitination. Researchers can use SD-36 to dissect the molecular mechanisms underlying targeted protein degradation and optimize the design of next-generation PROTACs.

1. Structure-based discovery of SD-36 as a potent, selective, and efficacious PROTAC degrader of STAT3 protein.

Zhou, H., Bai, L., Xu, R., Zhao, Y., Chen, J., McEachern, D., Chinnaswamy, K., Wen, B., Dai, L., Kumar, P. and Yang, C.Y., 2019. Journal of medicinal chemistry, 62(24), pp.11280-11300.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor and an attractive therapeutic target for cancer and other human diseases. Despite 20 years of persistent research efforts, targeting STAT3 has been very challenging. We report herein the structure-based discovery of potent small-molecule STAT3 degraders based upon the proteolysis targeting chimera (PROTAC) concept. We first designed SI-109 as a potent, small-molecule inhibitor of the STAT3 SH2 domain. Employing ligands for cereblon/cullin 4A E3 ligase and SI-109, we obtained a series of potent PROTAC STAT3 degraders, exemplified by SD-36. SD-36 induces rapid STAT3 degradation at low nanomolar concentrations in cells and fails to degrade other STAT proteins. SD-36 achieves nanomolar cell growth inhibitory activity in leukemia and lymphoma cell lines with high levels of phosphorylated STAT3. A single dose of SD-36 results in complete STAT3 protein degradation in xenograft tumor tissue and normal mouse tissues. SD-36 achieves complete and long-lasting tumor regression in the Molm-16 xenograft tumor model at well-tolerated dose-schedules. SD-36 is a potent, selective, and efficacious STAT3 degrader.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂