A senolytic peptide
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FOXO4-DRI Peptide (acetate)

Item No. 46425

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Synonyms
  • FOXO4-D-retro-inverso Peptide
Molecular Formula
C228H388N86O64 • XC2H4O2
Formula Weight
5358.1
Purity
≥95%
Formulation (Request formulation change)
A solid
Peptide Sequence
ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH
Solubility(Learn about Variance in Solubility)
PBS (pH 7.2): Sparingly soluble: 1-10 mg/ml
SMILES
CC[C@H]([C@@H](NC([C@H](NC([C@H](NC([C@H](NC([C@H]1CCCN1C([C@H](NC([C@H](NC([C@H](NC([C@H](NC([C@H](NC([C@H](N)CC(C)C)=O)[C@@H](O)C)=O)CC(C)C)=O)CCCNC(N)=N)=O)CCCCN)=O)CCC(O)=O)=O)=O)C)=O)CO)=O)CCC(O)=O)=O)C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(NCC(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(NCC(NCC(N[C@@H](C(N[C@@H](C(N2CCC[C@@H]2C(N3CCC[C@@H]3C(N4CCC[C@@H]4C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(N[C@@H](C(NCC(O)=O)=O)CCCNC(N)=N)=O)CCCCN)=O)CCCCN)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CCC(N)=O)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)=O)=O)=O)CCCNC(N)=N)=O)CCCCN)=O)=O)=O)CO)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CC(N)=O)=O)C)=O)CC5=CNC6=CC=CC=C65)=O)=O)CC(N)=O)=O)CCC(N)=O)=O)CO)=O)CC7=CC=C(O)C=C7)=O)C)=O)CCC(O)=O)=O)CC(C)C)=O)[C@@H](CC)C)=O)CO)=O)CCC(N)=O)=O)C)=O)C.CC(O)=O
InChi Code
InChI=1S/C228H388N86O64.C2H4O2/c1-16-115(9)174(308-201(361)145(70-76-171(331)332)295-207(367)155(109-316)304-180(340)119(13)276-210(370)158-58-38-92-311(158)216(376)147(71-77-172(333)334)298-196(356)132(47-23-27-81-232)284-192(352)137(53-33-87-264-224(249)250)290-203(363)149(98-114(7)8)303-214(374)176(121(15)319)310-181(341)126(233)96-112(3)4)212(372)277-120(14)177(337)280-141(66-72-162(234)321)200(360)306-157(111-318)209(369)309-175(116(10)17-2)213(373)302-148(97-113(5)6)204(364)293-144(69-75-170(329)330)185(345)274-117(11)178(338)299-150(99-122-62-64-124(320)65-63-122)205(365)307-156(110-317)208(368)294-143(68-74-164(236)323)199(359)301-152(101-165(237)324)183(343)272-106-169(328)279-151(100-123-103-269-127-43-19-18-42-125(123)127)202(362)275-118(12)179(339)300-153(102-166(238)325)206(366)291-138(54-34-88-265-225(251)252)193(353)288-139(55-35-89-266-226(253)254)197(357)305-154(108-315)184(344)271-104-167(326)270-105-168(327)278-129(44-20-24-78-229)186(346)297-146(57-37-91-268-228(257)258)215(375)313-94-40-60-160(313)218(378)314-95-41-61-161(314)217(377)312-93-39-59-159(312)211(371)296-140(56-36-90-267-227(255)256)195(355)287-134(50-30-84-261-221(243)244)190(350)286-136(52-32-86-263-223(247)248)194(354)292-142(67-73-163(235)322)198(358)289-135(51-31-85-262-222(245)246)191(351)285-133(49-29-83-260-220(241)242)189(349)283-131(46-22-26-80-231)188(348)282-130(45-21-25-79-230)187(347)281-128(48-28-82-259-219(239)240)182(342)273-107-173(335)336;1-2(3)4/h18-19,42-43,62-65,103,112-121,126,128-161,174-176,269,315-320H,16-17,20-41,44-61,66-102,104-111,229-233H2,1-15H3,(H2,234,321)(H2,235,322)(H2,236,323)(H2,237,324)(H2,238,325)(H,270,326)(H,271,344)(H,272,343)(H,273,342)(H,274,345)(H,275,362)(H,276,370)(H,277,372)(H,278,327)(H,279,328)(H,280,337)(H,281,347)(H,282,348)(H,283,349)(H,284,352)(H,285,351)(H,286,350)(H,287,355)(H,288,353)(H,289,358)(H,290,363)(H,291,366)(H,292,354)(H,293,364)(H,294,368)(H,295,367)(H,296,371)(H,297,346)(H,298,356)(H,299,338)(H,300,339)(H,301,359)(H
InChi Key
CCRGNZAUPFTMHX-WQBHTLCWSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    Product Description

    FOXO4-DRI peptide is a senolytic peptide corresponding to the D-retro-inverso sequence of amino acids 91-124 of forkhead box protein O4 (FOXO4) fused to the D-retro-inverso sequence of HIV Tat (48-59).1 It binds to transactivation domain 2 of p53 (p53TAD2; KD = 18.5 µM) and inhibits the protein-protein interaction between FOXO4 and p53 at 300 µM.1,2 FOXO4-DRI peptide selectively induces apoptosis in senescent IMR-90 fibroblasts over proliferating IMR-90 fibroblasts, as well as senescent A375 melanoma cells over proliferating A375 cells (IC50s = ~28 and >40 µM, respectively, for A375 cells).1,3 It protects against doxorubicin-induced liver toxicity in mice and decreases hair loss and increases physical activity in a mouse model of fast aging.1 FOXO4-DRI peptide induces apoptosis in senescent TM3 Leydig cells and increases serum testosterone levels in naturally aged male mice.4

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Baar, M.P., Brandt, R.M.C., Putavet, D.A., et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169(1), 132-147 (2017).

    2. Bourgeois, B., Spreitzer, E., Platero-Rochart, D., et al. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nat. Commun. 16(1), 5672 (2025).

    3. Le, H.H., Cinaroglu, S.S., Manalo, E.C., et al. Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells. EBioMedicine 73:103646, (2021).

    4. Zhang, C., Xie, Y., Chen, H., et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany N.Y.) 12(2), 1272-1284 (2020).