| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
S-adenosyl-L-homocysteine hydrolase (SAHH) (IC50 = 0.15 μM for enzyme activity inhibition) [1]
|
|---|---|
| ln Vitro |
The inhibitor of mixed lymphocyte reaction (MLR) responses is DZ2002 (0.1, 1, 10 µM; 96 hours) [1]. DZ2002 (0.1, 1, 10 µM; 24 hours) prevents human THP-1 cells and mouse peritoneal exudate cells from producing TNF-α and IL-12 [1]. On differentiated THP-1 cells, DZ2002 (0.1, 1, 10 µM; 64 hours) inhibits B7 (CD80/CD86) expression [1].
- DZ2002 exhibits potent SAHH inhibitory activity and immunosuppressive effects. It dose-dependently inhibited recombinant human SAHH activity with an IC50 of 0.15 μM. In mouse splenic lymphocytes, DZ2002 (0.1-10 μM) suppressed Concanavalin A (ConA)-induced T lymphocyte proliferation and Lipopolysaccharide (LPS)-induced B lymphocyte proliferation, with IC50 values of 0.8 μM and 1.2 μM, respectively. It also reduced the secretion of pro-inflammatory cytokines (IL-2, IFN-γ, TNF-α) from activated lymphocytes (ELISA assay) [1] - DZ2002 exerts anti-fibrotic and anti-inflammatory effects in vitro. In human dermal fibroblasts (HDFs) activated by TGF-β1, DZ2002 (0.5-5 μM) dose-dependently downregulated the expression of fibrosis-related markers (α-SMA, Col1A1, Col3A1) at both mRNA and protein levels (qPCR, Western blot). It also inhibited LPS-induced TNF-α and IL-6 production in human peripheral blood mononuclear cells (PBMCs) (ELISA) [2] |
| ln Vivo |
The DNFB-induced DTH response is blocked by DZ2002 (2, 10, 50 mg/kg; intraperitoneal injection; twice). (DNFB-induced DTH is a Th1 cell-mediated immunological response; macrophages have been demonstrated to play a significant part in this process and IL-12 is significantly produced) [1]. DZ2002 (0.08, 2 mg/kg; intraperitoneal injection; once daily for 7 days) substantially reduces the production of antibodies and delayed-type hypersensitivity reactions [1]. In SSc mice models, DZ2002 (50, 100 mg/kg; oral; once daily for 4 weeks) effectively inhibits the formation of collagen, promotes its breakdown, and controls the expression of many soluble factors. Fibrosis [2].
- In mouse models of , intraperitoneal injection of DZ2002 (10, 20 mg/kg/day) significantly prolonged the survival time of transplanted skin grafts. The 20 mg/kg dose extended graft survival from ~7 days (control) to ~18 days, accompanied by reduced infiltration of T lymphocytes and macrophages in graft tissues (immunohistochemistry) and decreased serum levels of IL-2 and IFN-γ (ELISA) [1] - In experimental systemic sclerosis (SSc) models (bleomycin-induced skin fibrosis and Tsk-1 mice), DZ2002 (15 mg/kg/day, intraperitoneal injection for 4 weeks) ameliorated skin fibrosis: reduced skin thickness, decreased collagen deposition (Masson's trichrome staining), and downregulated α-SMA and Col1A1 expression in skin tissues (Western blot). It also improved lung fibrosis, reduced pulmonary collagen content, and alleviated lung inflammation (HE staining, ELISA for TNF-α/IL-6). Additionally, it ameliorated vasculopathy by improving microvascular density and reducing vascular wall thickening in SSc mice [2] |
| Enzyme Assay |
- SAHH activity inhibition assay: Recombinant human SAHH was dissolved in reaction buffer containing its substrate S-adenosyl-L-homocysteine. DZ2002 (0.01-10 μM) was added, and the mixture was incubated at 37°C for 60 minutes. The reaction was terminated by adding trichloroacetic acid, and the amount of adenosine (product of SAHH-catalyzed reaction) was quantified by high-performance liquid chromatography (HPLC) to calculate the inhibition rate of SAHH activity. IC50 value was derived from dose-response curves [1]
|
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: BALB/c and C57BL/6 splenocytes (mitomycin C pre-treated; mixed lymphocytes) Tested Concentrations: 0.1, 1, 10 µM Incubation Duration: 96 hrs (hours) Experimental Results: MLR inhibition 24.5, 42.3 and 46.0% at doses of 0.1, 1 and 10 µM respectively. Cell viability assay[1] Cell Types: TG-stimulated mouse peritoneal macrophages and human THP-1 cells Tested Concentrations: 0.1, 1, 10 µM Incubation Duration: 24 hrs (hours) Experimental Results: Significant blocking of approximately 1800 pg/mL of IL -12 p40 production in untreated cells dropped to approximately 850 pg/ml at 10 µM and Dramatically diminished the active p70 form in untreated cells from approximately 1200 pg/mL to approximately 50 pg/mL. TNF-α levels were diminished by 45%. Cell viability assay[1] Cell Types: THP-1 Cell Tested Concentrations: 0.1, 1, 10 µM Incubation Duration: 64 hrs (hours) Experimental Results: CD80, especially CD86 expression was Dramatically downregulated in a dose-dependent manner. - Lymphocyte proliferation assay: Mouse splenic lymphocytes were isolated and seeded in 96-well plates. DZ2002 (0.1-10 μM) was added 1 hour before stimulation with ConA (for T cells) or LPS (for B cells). After 72 hours of incubation, cell proliferation was measured by MTT assay, and culture supernatants were collected for ELISA detection of IL-2, IFN-γ, and TNF-α [1] - Fibroblast activation assay: Human dermal fibroblasts (HDFs) were seeded in 6-well plates and activated with TGF-β1 (10 ng/mL) for 24 hours. DZ2002 (0.5-5 μM) was added, and cells were cultured for another 48 hours. Total RNA was extracted for qPCR analysis of Col1A1, Col3A1, and α-SMA mRNA levels; total proteins were extracted for Western blot detection of corresponding proteins [2] - PBMC cytokine production assay: Human PBMCs were isolated and treated with DZ2002 (0.5-5 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. ELISA was used to quantify TNF-α and IL-6 levels in supernatants [2] |
| Animal Protocol |
Animal/Disease Models: Male and female BALB/c and C57BL/6 mice (6 to 8 weeks old; DNFB-induced ear swelling model) [1].
Doses: 2, 10, 50 mg/kg Route of Administration: intraperitoneal (ip) injection; twice (1 hour before challenge and 24 hrs (hrs (hours)) after challenge) Experimental Results: Ear swelling was suppressed by 19.1%, 28.7% and 33.1%, respectively, in a dose-dependent manner . Animal/Disease Models: Male and female BALB/c and C57BL/6 mice (6 to 8 weeks old; DNFB-induced ear swelling model) [1]. Doses: 0.08, 2 mg/kg Route of Administration: intraperitoneal (ip) injection; single dose per day for 7 days. Experimental Results: Doses of 0.08 mg/kg and 2 mg/kg inhibited hemolysis by 24.5% and 18.4%, respectively, thereby reducing the production of anti-SRBC antibodies in the body. Animal/Disease Models: Wild-type C57BL/6 mice (8 to 12 weeks old; BLM-induced SSc mouse model) [2]. Doses: 50, 100 mg/kg Route of Administration: po (oral gavage); one time/day for 4 weeks. Experimental Results: BLM induced significant reductions in skin thickness and dermal thickness in mice. Dramatically diminished co - Allogeneic skin transplantation model: C57BL/6 mice (recipients) received skin grafts from BALB/c mice (donors). After transplantation, mice were randomly divided into control and DZ2002 treatment groups (10, 20 mg/kg/day). DZ2002 was dissolved in dimethyl sulfoxide (DMSO) and diluted with normal saline (final DMSO concentration ≤ 1%), administered via intraperitoneal injection once daily for 14 days. Graft survival time was recorded, and graft tissues were collected for immunohistochemistry; serum was collected for cytokine detection [1] - Systemic sclerosis models: 1) Bleomycin-induced skin fibrosis: C57BL/6 mice were subcutaneously injected with bleomycin (50 μg/day) for 4 weeks to induce SSc-like skin fibrosis. DZ2002 (15 mg/kg/day) was administered via intraperitoneal injection during weeks 2-4. 2) Tsk-1 mice (genetic SSc model): DZ2002 (15 mg/kg/day) was intraperitoneally injected for 4 weeks starting at 8 weeks of age. For both models, skin and lung tissues were collected for histopathological staining (HE, Masson's trichrome) and Western blot; serum was collected for ELISA [2] |
| References |
[1]. Wu QL, et al. Inhibition of S-adenosyl-L-homocysteine hydrolase induces immunosuppression. J Pharmacol Exp Ther. 2005 May;313(2):705-11.
[2]. Zhang Z, et al. DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models. Arthritis Res Ther. 2019 Dec 16;21(1):290. |
| Additional Infomation |
DZ2002 is a synthetic small molecule S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor[1][2]. Its core mechanism includes: inhibiting SAHH leading to the accumulation of intracellular S-adenosyl-L-homocysteine, thereby inhibiting methyltransferase activity and subsequent immune cell activation (immunosuppression)[1]; downregulating TGF-β1-mediated fibroblast activation and the production of pro-inflammatory cytokines, thereby alleviating fibrosis and inflammation (anti-fibrotic and anti-inflammatory effects)[2]. DZ2002 has shown potential therapeutic value in immune-related diseases (such as organ transplant rejection) and fibrosis-related autoimmune diseases (such as systemic sclerosis)[1][2].
|
| Molecular Formula |
C10H13N5O3
|
|---|---|
| Molecular Weight |
251.2419
|
| Exact Mass |
251.102
|
| CAS # |
33231-14-0
|
| PubChem CID |
11658872
|
| Appearance |
White to off-white solid powder
|
| LogP |
-0.5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
18
|
| Complexity |
303
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O([H])C([H])(C(=O)OC([H])([H])[H])C([H])([H])C([H])([H])N1C([H])=NC2=C(N([H])[H])N=C([H])N=C12
|
| InChi Key |
HNKGMGPCSSJYOT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C10H13N5O3/c1-18-10(17)6(16)2-3-15-5-14-7-8(11)12-4-13-9(7)15/h4-6,16H,2-3H2,1H3,(H2,11,12,13)
|
| Chemical Name |
methyl 4-(6-aminopurin-9-yl)-2-hydroxybutanoate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 61 mg/mL (~242.80 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9803 mL | 19.9013 mL | 39.8026 mL | |
| 5 mM | 0.7961 mL | 3.9803 mL | 7.9605 mL | |
| 10 mM | 0.3980 mL | 1.9901 mL | 3.9803 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
