Mongersen sodium targets SMAD7 mRNA, which encodes the SMAD7 protein. SMAD7 is an endogenous inhibitor of TGF‑beta1 signaling, acting as a negative feedback regulator. By binding to SMAD7 mRNA, the antisense oligonucleotide reduces SMAD7 protein levels, thereby restoring TGF‑beta1 anti‑inflammatory signaling. The compound targets the SMAD7 gene transcript, not a traditional protein receptor.

Mongersen sodium is evaluated for its ability to reduce SMAD7 protein expression in cultured cells (e.g., human colonic epithelial cells, fibroblasts). In vitro, treatment with Mongersen leads to dose‑dependent reduction of SMAD7 mRNA and protein levels, resulting in increased TGF‑beta1 signaling as measured by SMAD2/3 phosphorylation and transcriptional activity. No specific IC50 values are reported.

In vivo, Mongersen sodium (oral administration) alleviates Crohn‘s disease‑like experimental colitis in mice. It reduces intestinal inflammation, decreases inflammatory cytokine production (e.g., TNF‑alpha, IL‑6, IL‑1beta), and restores mucosal healing. The compound was evaluated in clinical trials for the treatment of Crohn‘s disease, where it showed efficacy in Phase 2 studies, but Phase 3 trials did not meet primary endpoints, and development was discontinued.

Mongersen sodium is an oligonucleotide that hybridizes to SMAD7 pre‑mRNA or mRNA. Binding affinity (Tm, KD) is measured by thermal denaturation (melting temperature) assays or surface plasmon resonance using complementary RNA sequences. The antisense oligonucleotide is incubated with a target RNA, and the stability of the duplex is assessed. No specific binding affinity value is provided in the sources. In vitro potency is assessed by measuring SMAD7 protein knockdown.

For in vitro SMAD7 knockdown assays, human cell lines (e.g., HT‑29, HeLa, or primary human intestinal fibroblasts) are seeded in 6‑well plates and treated with Mongersen sodium at graded concentrations (e.g., 1‑50 microM) for 24‑72 h. The oligonucleotide is delivered using a transfection reagent if needed, or for uptake studies, cells are treated without transfection to simulate oral delivery. SMAD7 protein levels are measured by Western blot or ELISA, and SMAD7 mRNA levels by qPCR.

For in vivo efficacy, female BALB/c mice (or other strains) are induced for colitis using dextran sulfate sodium (DSS) in drinking water or by transfer of CD4+CD45RBʰⁱ T cells. Mice are treated orally with Mongersen sodium at doses of 1‑50 mg/kg once daily for 7‑14 days. Disease activity index (DAI), colon length, and histological scores are assessed. Inflammatory cytokines in colonic tissue are measured by ELISA, and SMAD7 protein levels are assessed by Western blot or immunohistochemistry.

Mongersen sodium (C200H241N₆₉O10₇P20S20Na20, MW = 7044.00) is soluble in DMSO. The powder should be stored at 4degC sealed and away from moisture. For in vivo oral administration, it is formulated in water or phosphate‑buffered saline (PBS). After oral administration, Mongersen is distributed to the intestinal tract and is poorly absorbed systemically, which is desirable for local action in IBD. Detailed PK parameters (Cmax, Tmax, t1/2, AUC) are not provided in the sources.

In clinical trials, Mongersen sodium was generally well‑tolerated with no significant increase in adverse events compared to placebo. Common adverse events included mild‑to‑moderate nausea, headache, and nasopharyngitis. No serious treatment‑related adverse events were consistently reported. However, Phase 3 trials (REACH) did not meet primary endpoints, and development was discontinued. No preclinical toxicity data (LD50, target organ toxicity) are provided in the sources.

[1]. Monteleone G, et, al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. N Engl J Med. 2015 Mar 19;372(12):1104-13.

[2]. Knockdown of Smad7 With a Specific Antisense Oligonucleotide Attenuates Colitis and Colitis-Driven Colonic Fibrosis in Mice. Inflamm Bowel Dis. 2018 May 18;24(6):1213-1224.

Mongersen (GED‑0301) was an oral antisense oligonucleotide targeting SMAD7 that was developed by Celgene (now part of Bristol‑Myers Squibb) for the treatment of Crohn‘s disease. It received Fast Track designation from the FDA based on positive Phase 2 results. However, in Phase 3 clinical trials (REACH program), Mongersen did not achieve statistically significant improvement in clinical remission rates compared to placebo, and development was discontinued in 2019. The compound is for research use only and has not received regulatory approval for any indication. It serves as a valuable tool for studying SMAD7/TGF‑beta1 signaling in inflammation.

C200H241N69O107P20S20NA20

7044.00

7041.273

1443994-98-6

Mongersen; 1443994-46-4

121492864

Solid powder

27

139

122

436

19800

63

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=NC1=C9N=C(NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=C(C(=O)NC1=O)C)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=C(C(=O)NC1=O)C)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=C(C(=O)NC1=O)C)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=C(C(=NC1=O)N)C)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=NC2=C1N=C(NC2=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=NC2=C(N=CN=C21)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=NC2=C1N=C(NC2=O)N)OP(=S)([O-])OC[C@@H]1[C@H](C[C@@H](O1)N1C=CC(=NC1=O)N)O.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]

QWWDFWULNFYETN-ZPMFUBTDSA-A

InChI=1S/C200H261N69O107P20S20.20Na/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);;;;;;;;;;;;;;;;;;;;/q;20*+1/p-20/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

icosasodium;1-[(2R,4S,5R)-4-[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-oxidophosphinothioyl]oxyoxolan-2-yl]methoxy-oxidophosphinothioyl]oxy-5-[[[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-yl]oxy-oxidophosphinothioyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione

GED-0301 sodium

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ≥ 100 mg/mL

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)