mongersen   Click here for help

GtoPdb Ligand ID: 8277

Synonyms: DNA, d(P-thio)(G-T-m5C-G-C-C-C-C-T-T-C-T-C-C-C-m5C-G-C-A-G-C) | GED-0301 | GED0301
Immunopharmacology Ligand
Compound class: Nucleic acid
Comment: Mongersen (GED-0301) is a phosphorothioate single-stranded oligonucleotide matching the region 107-128 (5'-GCTGCGGGGAGAAGGGGCGAC-3') of the human Smad7 complementary DNA sequence. The antisense oligonucleotide sequence is (3'-5')d(P-thio)(G-T-m5C-G-C-C-C-C-T-T-C-T-C-C-C-m5C-G-C-A-G-C), where m5C represents 2'-deoxy-5-methyl-P-thiocytidylyl bases.
Formulated as a sodium adduct for therapeutic use (CID 121492864).
2D Structure
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SMILES / InChI / InChIKey
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Canonical SMILES CC1=CN([C@H]2C[C@@H]([C@@H](COP(=S)(O)O[C@H]3C[C@H](N4C=CC(=NC4=O)N)O[C@@H]3COP(=S)(O)O[C@H]5C[C@H](N6C=CC(=NC6=O)N)O[C@@H]5COP(=S)(O)O[C@H]7C[C@H](N8C=CC(=NC8=O)N)O[C@@H]7COP(=S)(O)O[C@H]9C[C@H](N%10C=C(C)C(=O)NC%10=O)O[C@@H]9COP(=S)(O)O[C@H]%11C[C@H](N%12C=CC(=NC%12=O)N)O[C@@H]%11COP(=S)(O)O[C@H]%13C[C@H](N%14C=C(C)C(=O)NC%14=O)O[C@@H]%13COP(=S)(O)O[C@H]%15C[C@H](N%16C=C(C)C(=O)NC%16=O)O[C@@H]%15COP(=S)(O)O[C@H]%17C[C@H](N%18C=CC(=NC%18=O)N)O[C@@H]%17COP(=S)(O)O[C@H]%19C[C@H](N%20C=CC(=NC%20=O)N)O[C@@H]%19COP(=S)(O)O[C@H]%21C[C@H](N%22C=CC(=NC%22=O)N)O[C@@H]%21COP(=S)(O)O[C@H]%23C[C@H](N%24C=CC(=NC%24=O)N)O[C@@H]%23COP(=S)(O)O[C@H]%25C[C@H](N%26C=NC%27=C%26N=C(N)NC%27=O)O[C@@H]%25COP(=S)(O)O[C@H]%28C[C@H](N%29C=C(C)C(=NC%29=O)N)O[C@@H]%28COP(=S)(O)O[C@H]%30C[C@H](N%31C=C(C)C(=O)NC%31=O)O[C@@H]%30COP(=S)(O)O[C@H]%32C[C@H](N%33C=NC%34=C%33N=C(N)NC%34=O)O[C@@H]%32CO)O2)OP(=S)(O)OC[C@@H]%35[C@H](C[C@H](N%36C=NC%37=C%36N=C(N)NC%37=O)O%35)OP(=S)(O)OC[C@@H]%38[C@H](C[C@H](N%39C=CC(=NC%39=O)N)O%38)OP(=S)(O)OC[C@@H]%40[C@H](C[C@H](N%41C=NC%42=C%41N=CN=C%42N)O%40)OP(=S)(O)OC[C@@H]%43[C@H](C[C@H](N%44C=NC%45=C%44N=C(N)NC%45=O)O%43)OP(=S)(O)OC[C@@H]%46[C@H](C[C@H](N%47C=CC(=NC%47=O)N)O%46)O)C(=O)N=C1N
Isomeric SMILES CC1=CN(C(=O)NC1=O)[C@H]2C[C@@H]([C@H](O2)COP(=S)(O)O[C@H]3C[C@@H](O[C@@H]3CO)N4C=NC5=C4N=C(NC5=O)N)OP(=S)(O)OC[C@@H]6[C@H](C[C@@H](O6)N7C=C(C(=NC7=O)N)C)OP(=S)(O)OC[C@@H]8[C@H](C[C@@H](O8)N9C=NC%10=C9N=C(NC%10=O)N)OP(=S)(O)OC[C@@H]%11[C@H](C[C@@H](O%11)N%12C=CC(=NC%12=O)N)OP(=S)(O)OC[C@@H]%13[C@H](C[C@@H](O%13)N%14C=CC(=NC%14=O)N)OP(=S)(O)OC[C@@H]%15[C@H](C[C@@H](O%15)N%16C=CC(=NC%16=O)N)OP(=S)(O)OC[C@@H]%17[C@H](C[C@@H](O%17)N%18C=CC(=NC%18=O)N)OP(=S)(O)OC[C@@H]%19[C@H](C[C@@H](O%19)N%20C=C(C(=O)NC%20=O)C)OP(=S)(O)OC[C@@H]%21[C@H](C[C@@H](O%21)N%22C=C(C(=O)NC%22=O)C)OP(=S)(O)OC[C@@H]%23[C@H](C[C@@H](O%23)N%24C=CC(=NC%24=O)N)OP(=S)(O)OC[C@@H]%25[C@H](C[C@@H](O%25)N%26C=C(C(=O)NC%26=O)C)OP(=S)(O)OC[C@@H]%27[C@H](C[C@@H](O%27)N%28C=CC(=NC%28=O)N)OP(=S)(O)OC[C@@H]%29[C@H](C[C@@H](O%29)N%30C=CC(=NC%30=O)N)OP(=S)(O)OC[C@@H]%31[C@H](C[C@@H](O%31)N%32C=CC(=NC%32=O)N)OP(=S)(O)OC[C@@H]%33[C@H](C[C@@H](O%33)N%34C=C(C(=NC%34=O)N)C)OP(=S)(O)OC[C@@H]%35[C@H](C[C@@H](O%35)N%36C=NC%37=C%36N=C(NC%37=O)N)OP(=S)(O)OC[C@@H]%38[C@H](C[C@@H](O%38)N%39C=CC(=NC%39=O)N)OP(=S)(O)OC[C@@H]%40[C@H](C[C@@H](O%40)N%41C=NC%42=C(N=CN=C%42%41)N)OP(=S)(O)OC[C@@H]%43[C@H](C[C@@H](O%43)N%44C=NC%45=C%44N=C(NC%45=O)N)OP(=S)(O)OC[C@@H]%46[C@H](C[C@@H](O%46)N%47C=CC(=NC%47=O)N)O
InChI InChI=1S/C200H261N69O107P20S20/c1-81-48-259(195(290)235-165(81)211)149-38-98(367-392(311,412)333-73-127-107(47-159(355-127)269-80-224-164-172(269)240-184(217)244-180(164)279)376-395(314,415)326-64-118-97(37-148(346-118)258-26-16-138(210)234-194(258)289)366-387(306,407)332-71-125-104(44-155(353-125)265-76-220-160-167(213)218-75-219-168(160)265)374-396(315,416)335-72-126-105(45-157(354-126)267-78-222-162-170(267)238-182(215)242-178(162)277)373-377(296,397)316-55-109-87(271)27-139(337-109)249-17-7-129(201)225-185(249)280)119(347-149)66-327-384(303,404)363-94-34-145(255-23-13-135(207)231-191(255)286)341-113(94)59-321-380(299,400)359-91-31-142(252-20-10-132(204)228-188(252)283)339-111(91)57-319-382(301,402)361-92-32-143(253-21-11-133(205)229-189(253)284)343-115(92)61-323-388(307,408)369-101-41-152(262-51-84(4)174(273)246-198(262)293)350-122(101)68-328-386(305,406)365-96-36-147(257-25-15-137(209)233-193(257)288)344-116(96)62-324-389(308,409)370-102-42-153(263-52-85(5)175(274)247-199(263)294)352-124(102)70-331-391(310,411)372-103-43-154(264-53-86(6)176(275)248-200(264)295)351-123(103)69-329-385(304,405)364-95-35-146(256-24-14-136(208)232-192(256)287)342-114(95)60-322-381(300,401)360-90-30-141(251-19-9-131(203)227-187(251)282)338-110(90)56-318-379(298,399)358-89-29-140(250-18-8-130(202)226-186(250)281)340-112(89)58-320-383(302,403)362-93-33-144(254-22-12-134(206)230-190(254)285)345-117(93)63-325-394(313,414)375-106-46-158(268-79-223-163-171(268)239-183(216)243-179(163)278)356-128(106)74-334-393(312,413)368-99-39-150(260-49-82(2)166(212)236-196(260)291)348-120(99)67-330-390(309,410)371-100-40-151(261-50-83(3)173(272)245-197(261)292)349-121(100)65-317-378(297,398)357-88-28-156(336-108(88)54-270)266-77-221-161-169(266)237-181(214)241-177(161)276/h7-26,48-53,75-80,87-128,139-159,270-271H,27-47,54-74H2,1-6H3,(H,296,397)(H,297,398)(H,298,399)(H,299,400)(H,300,401)(H,301,402)(H,302,403)(H,303,404)(H,304,405)(H,305,406)(H,306,407)(H,307,408)(H,308,409)(H,309,410)(H,310,411)(H,311,412)(H,312,413)(H,313,414)(H,314,415)(H,315,416)(H2,201,225,280)(H2,202,226,281)(H2,203,227,282)(H2,204,228,283)(H2,205,229,284)(H2,206,230,285)(H2,207,231,286)(H2,208,232,287)(H2,209,233,288)(H2,210,234,289)(H2,211,235,290)(H2,212,236,291)(H2,213,218,219)(H,245,272,292)(H,246,273,293)(H,247,274,294)(H,248,275,295)(H3,214,237,241,276)(H3,215,238,242,277)(H3,216,239,243,278)(H3,217,240,244,279)/t87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108+,109+,110+,111+,112+,113+,114+,115+,116+,117+,118+,119+,120+,121+,122+,123+,124+,125+,126+,127+,128+,139+,140+,141+,142+,143+,144+,145+,146+,147+,148+,149+,150+,151+,152+,153+,154+,155+,156+,157+,158+,159+,377?,378?,379?,380?,381?,382?,383?,384?,385?,386?,387?,388?,389?,390?,391?,392?,393?,394?,395?,396?/m0/s1
InChI Key ABASMUXUCSQFKC-PKEKLUKKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

References
1. Boirivant M, Pallone F, Di Giacinto C, Fina D, Monteleone I, Marinaro M, Caruso R, Colantoni A, Palmieri G, Sanchez M et al.. (2006)
Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis.
Gastroenterology, 131 (6): 1786-98. [PMID:17087939]
2. Monteleone G, Kumberova A, Croft NM, McKenzie C, Steer HW, MacDonald TT. (2001)
Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease.
J Clin Invest, 108 (4): 601-9. [PMID:11518734]
3. Monteleone G, Neurath MF, Ardizzone S, Di Sabatino A, Fantini MC, Castiglione F, Scribano ML, Armuzzi A, Caprioli F, Sturniolo GC et al.. (2015)
Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease.
N Engl J Med, 372 (12): 1104-13. [PMID:25785968]
4. Trivedi PJ, Adams DH. (2018)
Chemokines and Chemokine Receptors as Therapeutic Targets in Inflammatory Bowel Disease; Pitfalls and Promise.
J Crohns Colitis, 12 (suppl_2): S641-S652. [PMID:30137309]