xStAx-VHLL

Selective peptide-based β-catenin Degrader (PROTAC®). Comprises a β-catenin-targeted stapled peptide, xStAx, linked to a VHL-binding peptide. Reduces β-catenin levels in HEK293T cells and colorectal cancer cell lines. Selectively degrades β-catenin over other Wnt signaling pathway components. Inhibits tumor growth in APCmin/+ mice, with constitutively active Wnt signaling, and reduces survival of patient-derived colorectal cancer cell organoids.

Product information

Molecular Weight: 3231.89

Formula: C154H244N48O29

Chemical Name: 2-((3S, 6S, 9S, 12S, 21S, Z)-21-((2S, 5S, 8S, 18S, 21S, 24S, 27S, 30S, 33S, 36S)-21-((1H-indol-3-yl)methyl)-1-((S)-2-((S)-1-((2S, 3S)-1-((S)-2-carbamoylpyrrolidin-1-yl)-3-methyl-1-oxopentan-2-ylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-ylcarbamoyl)pyrrolidin-1-yl)-18, 27, 30-tris(3-guanidinopropyl)-37-(1H-imidazol-5-yl)-5-isobutyl-24, 33-diisopropyl-2, 8-dimethyl-1, 4, 7, 10, 17, 20, 23, 26, 29, 32, 35-undecaoxo-3, 6, 9, 16, 19, 22, 25, 28, 31, 34-decaazaheptatriacontan-36-ylcarbamoyl)-12-((S)-2-((S)-1-((S)-2-((S)-2-((S)-2-acetamido-5-guanidinopentanamido)-5-guanidinopentanamido)-3-(1H-indol-3-yl)propanoyl)pyrrolidine-2-carboxamido)-5-guanidinopentanamido)-9-sec-butyl-6-isobutyl-12, 21-dimethyl-2, 5, 8, 11-tetraoxo-1, 4, 7, 10-tetraazacyclohenicos-16-en-3-yl)acetic acid

Smiles: CC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@]1(C)CCCC=CCCC[C@](C)(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCCCCCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1CCC[C@H]1C(N)=O |c:66|

InChiKey: NYZLXWJSWCBINW-OBGJTUHRSA-N

InChi: InChI=1S/C154H244N48O29/c1-18-87(11)121-141(226)190-108(73-84(5)6)131(216)188-112(78-118(206)207)136(221)199-153(16,60-30-22-20-21-23-31-61-154(17,146(231)197-121)198-135(220)106(51-38-68-175-152(166)167)185-137(222)116-54-41-71-202(116)143(228)113(76-94-80-177-100-45-29-27-43-98(94)100)192-128(213)103(48-35-65-172-149(160)161)183-126(211)102(181-91(15)203)47-34-64-171-148(158)159)145(230)193-111(77-95-81-168-82-178-95)134(219)195-119(85(7)8)139(224)186-104(49-36-66-173-150(162)163)127(212)184-105(50-37-67-174-151(164)165)129(214)194-120(86(9)10)140(225)191-110(75-93-79-176-99-44-28-26-42-97(93)99)132(217)182-101(46-33-63-170-147(156)157)125(210)169-62-32-24-25-55-117(205)179-89(13)124(209)187-107(72-83(3)4)130(215)180-90(14)142(227)201-70-40-53-115(201)138(223)189-109(74-92-56-58-96(204)59-57-92)133(218)196-122(88(12)19-2)144(229)200-69-39-52-114(200)123(155)208/h20-21,26-29,42-45,56-59,79-90,101-116,119-122,176-177,204H,18-19,22-25,30-41,46-55,60-78H2,1-17H3,(H2,155,208)(H,168,178)(H,169,210)(H,179,205)(H,180,215)(H,181,203)(H,182,217)(H,183,211)(H,184,212)(H,185,222)(H,186,224)(H,187,209)(H,188,216)(H,189,223)(H,190,226)(H,191,225)(H,192,213)(H,193,230)(H,194,214)(H,195,219)(H,196,218)(H,197,231)(H,198,220)(H,199,221)(H,206,207)(H4,156,157,170)(H4,158,159,171)(H4,160,161,172)(H4,162,163,173)(H4,164,165,174)(H4,166,167,175)/b21-20-/t87-,88-,89-,90-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,119-,120-,121-,122-,153-,154-/m0/s1

Technical Data

Appearance: Solid Power

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

Solubility: Soluble to 1 mg/ml in water

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

References:

1. Liao, Hongwei & Li, Xiang & Zhao, Lianzheng & Wang, Yalong & Wang, Xiaodan & Wu, Ye & Zhou, Xin & Fu, Wei & Liu, Lei & Hu, Hong-Gang & Chen, Ye-Guang. (2020). A PROTAC peptide induces durable β-catenin degradation and suppresses Wnt-dependent intestinal cancer. Cell Discovery. 6. 10.1038/s41421-020-0171-1.

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