| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
- Mastermind-like 1 (MAML1) (direct binding to inhibit Notch signaling) [2]
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|---|---|
| ln Vitro |
- Notch Pathway Inhibition: SAHM1 suppressed Notch reporter gene activity in HEK293 cells transfected with a Notch-responsive luciferase construct. The compound reduced luciferase expression by 65% at 1 μM, indicating dose-dependent inhibition of Notch signaling [2]
- Th2 Cytokine Reduction: In human peripheral blood mononuclear cells (PBMCs), SAHM1 decreased IL-4 and IL-13 production by 40–50% at 0.5 μM, blocking Th2 polarization [2] |
| ln Vivo |
- Asthma Symptom Improvement: In a mouse model of allergic asthma, SAHM1 (10 mg/kg, intranasal) significantly reduced eosinophil infiltration in bronchoalveolar lavage fluid (BALF) by 70% compared to vehicle controls. Airway hyperresponsiveness (AHR) was also attenuated, with a 50% decrease in methacholine-induced lung resistance [2]
- Mucus Hypersecretion Suppression: Treatment with SAHM1 decreased mucus-producing goblet cells in the airway epithelium by 60%, as assessed by periodic acid-Schiff (PAS) staining [2] |
| Enzyme Assay |
- MAML1 Binding Assay: Recombinant MAML1 protein was incubated with SAHM1 (0.1–10 μM) in a buffer containing Tris-HCl (pH 7.5) and NaCl. Binding affinity was determined using surface plasmon resonance (SPR), revealing a KD of 0.8 μM. The compound competed with Notch intracellular domain (NICD) for MAML1 binding, as shown by displacement assays [2]
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| Cell Assay |
- T Cell Polarization Assay: Naive CD4+ T cells were activated with anti-CD3/CD28 beads and differentiated into Th2 cells in the presence of SAHM1 (0.1–1 μM). Flow cytometry analysis showed a dose-dependent reduction in GATA3+ cells (from 35% to 18%) and IL-4 production [2]
- Airway Smooth Muscle Cell Proliferation: SAHM1 (1–10 μM) inhibited PDGF-induced proliferation of human airway smooth muscle cells (HASMCs) by 30–40%, as measured by BrdU incorporation [2] |
| Animal Protocol |
- Asthma Model: BALB/c mice were sensitized with ovalbumin (OVA) and challenged with aerosolized OVA to induce allergic asthma. SAHM1 (10 mg/kg) or vehicle was administered intranasally daily for 7 days starting 24 hours after the final challenge. BALF and lung tissues were collected for analysis [2]
- Formulation: SAHM1 was dissolved in sterile saline containing 0.1% DMSO and administered via intranasal drops [2] |
| ADME/Pharmacokinetics |
Bioavailability: After intranasal administration to mice, the plasma concentration (Cₘₐₓ) of SAHM1 in lung tissue reached 2.5 μM within 1 hour. The half-life of this compound in the respiratory tract is 4 hours [2]. Distribution: Systemic distribution is limited, with less than 5% of the dose detected in plasma. SAHM1 mainly accumulates in the lungs [2].
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| Toxicity/Toxicokinetics |
Acute toxicity: No deaths or significant adverse reactions were observed in mice treated with SAHM1 via intranasal administration at doses up to 100 mg/kg. Histological examination of major organs revealed no signs of toxicity.[2] - Inflammatory biomarkers: No changes in liver enzymes (ALT, AST) or renal function markers (BUN, creatinine) were detected in treated animals, indicating no systemic toxicity.[2]
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| References |
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| Additional Infomation |
- Mechanism of action: SAHM1 disrupts the Notch-MAML1-CSL transcriptional complex, thereby preventing the expression of Notch target genes. This inhibition blocks Th2 cell differentiation and airway remodeling [2] - Therapeutic potential: SAHM1 represents a novel approach to treating asthma by targeting immune and structural components of asthma [2] - Stability: Its unique α-helix structure enhances its resistance to proteolysis, enabling it to remain active in vivo [2]
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| Molecular Formula |
C96H163N36F3O25S
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|---|---|
| Molecular Weight |
2310.60
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| Related CAS # |
SAHM1;2050906-89-1
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| Sequence |
Ac-beta-Ala-Glu-Arg-Leu-Arg-Arg-Arg-Ile-S5-Leu-Cys-Arg-S5-His-His-Ser-Thr（stapled on S5&S5）
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
-5.2
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| SMILES |
CC[C@H](C)[C@@H](C(=O)N[C@]1(CCC/C=C\CCC[C@@](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC1=O)CC(C)C)CS)CCCNC(=N)N)(C)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC3=CNC=N3)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)C
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| InChi Key |
ADWKVIAAKDSBNE-VHQDTIAVSA-N
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| InChi Code |
InChI=1S/C94H162N36O23S/c1-12-50(6)69(127-76(141)59(27-22-36-110-91(101)102)118-72(137)56(24-19-33-107-88(95)96)116-73(138)57(25-20-34-108-89(97)98)119-77(142)62(38-48(2)3)121-74(139)58(26-21-35-109-90(99)100)117-75(140)61(29-30-68(134)135)115-71(136)51(7)114-53(9)133)84(149)130-94(11)32-18-16-14-13-15-17-31-93(10,129-83(148)60(28-23-37-111-92(103)104)120-82(147)67(45-154)124-78(143)63(39-49(4)5)125-87(94)153)86(152)126-65(41-55-43-106-47-113-55)80(145)122-64(40-54-42-105-46-112-54)79(144)123-66(44-131)81(146)128-70(52(8)132)85(150)151/h13-14,42-43,46-52,56-67,69-70,131-132,154H,12,15-41,44-45H2,1-11H3,(H,105,112)(H,106,113)(H,114,133)(H,115,136)(H,116,138)(H,117,140)(H,118,137)(H,119,142)(H,120,147)(H,121,139)(H,122,145)(H,123,144)(H,124,143)(H,125,153)(H,126,152)(H,127,141)(H,128,146)(H,129,148)(H,130,149)(H,134,135)(H,150,151)(H4,95,96,107)(H4,97,98,108)(H4,99,100,109)(H4,101,102,110)(H4,103,104,111)/b14-13-/t50-,51-,52+,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,69-,70-,93-,94-/m0/s1
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| Chemical Name |
(4S)-4-[[(2S)-2-acetamidopropanoyl]amino]-5-[[(2S)-5-carbamimidamido-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(2S,3S)-1-[[(3S,6R,9S,12S,16Z,21S)-3-(3-carbamimidamidopropyl)-21-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]carbamoyl]-12,21-dimethyl-9-(2-methylpropyl)-2,5,8,11-tetraoxo-6-(sulfanylmethyl)-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
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| Synonyms |
SAHM1 TFA; SAHM 1 TFA;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.4328 mL | 2.1639 mL | 4.3279 mL | |
| 5 mM | 0.0866 mL | 0.4328 mL | 0.8656 mL | |
| 10 mM | 0.0433 mL | 0.2164 mL | 0.4328 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.
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