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| 25mg |
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Purity: ≥98%
Super-TDU is a rationally designed peptide-based inhibitor targeting the YAP-TEADs interaction by mimicking the VGLL with anticancer activity. VGLL4 is a previously identified YAP antagonist which also functions as a regulator of Wnt/β-catenin signalling. Super-TDU demonstrated therapeutic potentials for treating human cancer with YAP-activation. It reduced endogenous interaction between YAP and TEADs as shown by coIP experiment. Super-TDU inhibited cell viability and colony formation of GC cell lines MGC-803, BGC-823, and HGC27, but not MKN-45 as predicted. Moreover, the Super-TDU downregulated expression of YAP-TEADs target genes CTGF, CYR61, and CDX2. Further chromatin immunoprecipitation (ChIP) assays also showed that the Super-TDU dose-dependently reduced the amount of CTGF and CDX2 promoter cDNA ChIPed by YAP antibody. To verify the specificity of the Super-TDU, two Super-TDU mutants were created which harbor mutations that disable TEADs binding. As expected, the mutant Super-TDUs failed to interact with TEADs and inhibit cell proliferation. Thus the Super-TDU appears to have a broad but specific antitumor activity toward YAP-driven human cancers in which YAP/VGLL4 ratio should be considered as an important prognostic marker for personalized treatment.
| ln Vitro |
Super-TDU inhibits the expression of CTGF, CYR61, and CDX2, the target genes of YAP-TEADs. GC cell lines MGC-803, BGC-823, and HGC27 exhibit reduced colony formation and cell survival when exposed to Super-TDU [1].
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| ln Vivo |
Super-TDU, administered intravenously once a day at doses of 50 μg/kg or 500 μg/kg, greatly lowers the size, weight, and YAP target genes of mice tumors [1]. The CLs for Super-TDU (iv; 250 μg/kg and 500 μg/kg) mice are 7.41 mL/min/kg and 7.72 mL/min/kg, respectively; Cmax values are 6.12 ng/mL and 13.3 ng/mL. The t1/2α for the mice is 0.78 hours and 0.82 hours, respectively[1].
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| Animal Protocol |
Animal/Disease Models: BALB/cA nu/nu (nude) mice[1]
Doses: 50 μg/kg or 500 μg/kg Route of Administration: intravenous (iv) Injection; per day Experimental Results: diminished the sizes, weights of tumors, and YAP target genes in a dose-dependent manner. Animal/Disease Models: BALB/cA nu/nu (nude) mice[1] Doses: 250 μg/kg or 500 μg/kg (pharmacokinetic/PK Study) Route of Administration: intravenous (iv) Injection Experimental Results: The t1/2α is 0.78 hrs (hours) and 0.82 hrs (hours); the Cmax is 6.12 ng/mL and 13.3 ng/mL; the CL is7.41 ml/min/kg and 7.72 ml/min/kg for 250 μg/kg and 500 μg/kg in mice, respectively. |
| References |
| Molecular Formula |
C237H370N66O69S
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|---|---|---|
| Molecular Weight |
5279.9396
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| Exact Mass |
5278.726
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| CAS # |
1599441-71-0
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| Related CAS # |
Super-TDU TFA
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| PubChem CID |
155886330
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| Appearance |
White to off-white solid powder
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| LogP |
-25.5
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| Hydrogen Bond Donor Count |
71
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| Hydrogen Bond Acceptor Count |
81
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| Rotatable Bond Count |
173
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| Heavy Atom Count |
373
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| Complexity |
13400
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C)CCC(C(NC(C(NC(C(NC(CCCNC(=N)N)C(NC(CCCCN)C(NC(CC(C)C)C(N1CCCC1C(NC(CC(=O)O)C(NC(CO)C(NC(CC1C=CC=CC=1)C(NC(CC1C=CC=CC=1)C(NC(CCCCN)C(N1CCCC1C(N1CCCC1C(NC(C(N)=O)CCC(=O)O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)CC(C)C)=O)CCCNC(=N)N)=O)NC(C1CCCN1C(C(C(C)C)NC(C(C(C)O)NNC(CCC(N)=O)C(C(C1CCCN1C(C(C(C)C)NC(C(CC(N)=O)NC(C(C)NC(C(C(C)O)NC(C(CCCCN)NC(C1CCCN1C(C(CC(N)=O)NC(CNC(C(CO)NC(CNC(CNC(C(C(C)CC)NC(C(CCC(N)=O)NC(C(CC(C)C)NC(C(CC1=CNC2=CC=CC=C12)NC(C(C(C)O)NC(C(CC(=O)O)NC(CNC(C(CC(C)C)NC(C(CO)NC(C(CCCCN)NC(C(C)NC(C(CC1C=CC=CC=1)NC(C(CC1=CN=CN1)NC(C(CC(=O)O)NC(C(CC(=O)O)NC(C(C(C)C)NNC(C=O)CO)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O
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| InChi Key |
VNAMPXYTTUOEFP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C237H370N66O69S/c1-23-125(16)189(291-206(343)146(72-75-174(243)313)270-209(346)151(93-120(6)7)277-212(349)155(98-134-106-254-138-58-34-33-57-137(134)138)284-228(365)191(129(20)310)293-218(355)158(102-182(322)323)262-179(318)110-256-198(335)149(91-118(2)3)275-219(356)165(115-307)287-203(340)141(59-35-39-78-238)266-196(333)126(17)260-207(344)152(95-131-51-27-24-28-52-131)278-213(350)156(99-135-107-251-117-259-135)281-214(351)159(103-183(324)325)282-215(352)161(105-185(328)329)285-226(363)186(122(10)11)296-294-136(112-304)113-305)225(362)258-108-177(316)255-109-178(317)264-164(114-306)199(336)257-111-180(319)263-163(101-176(245)315)232(369)300-86-46-66-168(300)222(359)271-143(61-37-41-80-240)205(342)292-190(128(19)309)227(364)261-127(18)197(334)274-157(100-175(244)314)217(354)289-187(123(12)13)234(371)298-84-45-65-167(298)194(331)193(330)139(71-74-173(242)312)295-297-192(130(21)311)229(366)290-188(124(14)15)235(372)302-88-49-69-171(302)223(360)272-147(77-90-373-22)204(341)268-145(64-44-83-253-237(249)250)201(338)276-150(92-119(4)5)208(345)269-144(63-43-82-252-236(247)248)200(337)267-142(60-36-40-79-239)202(339)286-162(94-121(8)9)231(368)299-85-47-67-169(299)224(361)283-160(104-184(326)327)216(353)288-166(116-308)220(357)280-154(97-133-55-31-26-32-56-133)211(348)279-153(96-132-53-29-25-30-54-132)210(347)273-148(62-38-42-81-241)230(367)303-89-50-70-172(303)233(370)301-87-48-68-170(301)221(358)265-140(195(246)332)73-76-181(320)321/h24-34,51-58,106-107,112,117-130,136,139-172,186-192,254,294-297,305-311H,23,35-50,59-105,108-111,113-116,238-241H2,1-22H3,(H2,242,312)(H2,243,313)(H2,244,314)(H2,245,315)(H2,246,332)(H,251,259)(H,255,316)(H,256,335)(H,257,336)(H,258,362)(H,260,344)(H,261,364)(H,262,318)(H,263,319)(H,264,317)(H,265,358)(H,266,333)(H,267,337)(H,268,341)(H,269,345)(H,270,346)(H,271,359)(H,272,360)(H,273,347)(H,274,334)(H,275,356)(H,276,338)(H,277,349)(H,278,350)(H,279,348)(H,280,357)(H,281,351)(H,282,352)(H,283,361)(H,284,365)(H,285,363)(H,286,339)(H,287,340)(H,288,353)(H,289,354)(H,290,366)(H,291,343)(H,292,342)(H,293,355)(H,320,321)(H,322,323)(H,324,325)(H,326,327)(H,328,329)(H4,247,248,252)(H4,249,250,253)
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| Chemical Name |
5-amino-4-[[1-[1-[6-amino-2-[[2-[[2-[[2-[[2-[[1-[2-[[6-amino-2-[[2-[[2-[[2-[[2-[[1-[2-[[2-[2-[6-amino-1-[1-[2-[[4-amino-2-[2-[[2-[[6-amino-2-[[1-[4-amino-2-[[2-[[2-[[2-[[2-[[2-[[5-amino-2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[6-amino-2-[2-[[2-[[2-[[3-carboxy-2-[[3-carboxy-2-[[2-[2-(1-hydroxy-3-oxopropan-2-yl)hydrazinyl]-3-methylbutanoyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]amino]propanoylamino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]propanoylamino]-4-oxobutanoyl]amino]-3-methylbutanoyl]pyrrolidin-2-yl]-1,2,6-trioxohexan-3-yl]hydrazinyl]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 25 mg/mL (4.73 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1894 mL | 0.9470 mL | 1.8940 mL | |
| 5 mM | 0.0379 mL | 0.1894 mL | 0.3788 mL | |
| 10 mM | 0.0189 mL | 0.0947 mL | 0.1894 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Downregulation ofVGLL4Was Associated with Upregulation of YAP Target Genes and GC Prognosis.Cancer Cell.2014 Feb 10;25(2):166-80. |
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VGLL4 Inhibits Gastric Tumor Cell Growth through Inhibiting YAP-Induced TEAD4 Transactivation.Cancer Cell.2014 Feb 10;25(2):166-80. |
Crystal Structure of VGLL4-TEAD4 Complex.Cancer Cell.2014 Feb 10;25(2):166-80. |
The Tandem TDU Domains of VGLL4 Are Sufficient to Inhibit YAP Activity.Cancer Cell.2014 Feb 10;25(2):166-80. |
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TheSuper-TDUPotently Inhibits Gastric Tumor Growth.Cancer Cell.2014 Feb 10;25(2):166-80. |
TheSuper-TDUInhibits Human Primary GC Growth and GC Tumorigenesis in theH.pylori-Infected Mouse Model.Cancer Cell.2014 Feb 10;25(2):166-80. |
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