SD-36 is a potent and efficacious PROTAC STAT3 degrader (Kd=~50 nM), and demonstrates high selectivity over other STAT members. SD-36 also effectively degrades mutated STAT3 proteins in cells and suppresses the transcriptional activity of STAT3 (IC50=10 nM). SD-36 exerts robust anti-tumor activity, and achieves complete and long-lasting tumor regression in mouse tumor models. SD-36 is composed of the STAT3 inhibitor SI-109, a linker, and an analog of CRBN ligand Lenalidomide for E3 ubiquitin ligase.

Product information

Molecular Weight: 1158.15

Formula: C59H62F2N9O12P

Chemical Name: [(2-{[(5S,8S,10aR)-8-{[(1S)-3-carbamoyl-1-[(diphenylmethyl)carbamoyl]propyl]carbamoyl}-3-{8-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-yl]oct-7-ynoyl}-6-oxo-decahydropyrrolo[1,2-a][1,5]diazocin-5-yl]carbamoyl}-1H-indol-5-yl)difluoromethyl]phosphonic acid

Smiles: NC(=O)CC[C@H](NC(=O)[C@@H]1CC[C@@H]2CCN(C[C@H](NC(=O)C3=CC4=CC(=CC=C4N3)C(F)(F)P(O)(O)=O)C(=O)N21)C(=O)CCCCCC#CC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O)C(=O)NC(C1C=CC=CC=1)C1C=CC=CC=1

InChiKey: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 150 mg/mL (129.52 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

SD-36 inhibits the growth of a subset of acute myeloid leukemia and anaplastic large-cell lymphoma cell lines by inducing cell-cycle arrest and/or apoptosis. SD-36 (0.005-5 μM; 4 days) demonstrates potent activity (IC50＜2 μM) in MOLM-16, DEL, Karpas-299, KI-JK, SU-DHL-I, SUP-M2 cell lines. SD-36 (1 μM; 5 hours) completely depletes both monomeric and dimeric STAT3 protein in MOLM-16 cells.

In Vivo:

SD-36 (25-100 mg/kg; i.v.; weekly dosing for 4 weeks) achieves complete and long-lasting tumor regression in mice. SD-36 effectively inhibits tumor growth at 25 and 50 mg/kg administered on day 1, 3, and 5 per week and achieved complete tumor regression at 100 mg/kg with the same schedule in the SU-DHL-1 xenograft model. SD-36 at 50 mg/kg 3 times per week completely inhibits tumor growth in the SUP-M2 tumor model.

Products are for research use only. Not for human use.