| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
Glucocorticoid receptor (GR); Hydrocortisone hemisuccinate exerts its pharmacological effects by binding to the cytosolic glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. Upon binding, the receptor-ligand complex translocates to the cell nucleus, where it binds to glucocorticoid response elements (GREs) in the promoter regions of target genes, leading to increased transcription of genes encoding anti-inflammatory mediators. A key mechanism involves the induction of lipocortins (annexins), which inhibit cytosolic phospholipase A2 (cPLA2). This inhibition prevents the release of arachidonic acid from cell membrane phospholipids, thereby blocking the biosynthesis of prostaglandins and leukotrienes—both potent inflammatory mediators. Additionally, hydrocortisone hemisuccinate suppresses the expression of pro-inflammatory cytokines including IL-6 and IL-3, with IC50 values of 6.7 μM and 21.4 μM, respectively. The compound also inhibits the response of T lymphocytes and peripheral lymphocyte cultures to phytohemagglutinin (PHA).
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| ln Vitro |
Hydrocortisone hemisuccinate has no deleterious effect on MH60 cells that are IL-6-independent, but it inhibits the biological activities of IL-6 and IL-3 with IC50 values of 6.7 and 21.4 μM, respectively [3]. Hydrocortisone hemisuccinate (0.12-60 μM; 72 hours) suppresses T lymphocyte and peripheral lymphocyte cultures' responses to phytohemagglutinin (PHA) [3].
Suppressed IL-6-dependent proliferation of MH60.BSF2 cells (IC₅₀ = 3.5 × 10⁻⁷ M)[1] Inhibited lymphocyte proliferation in human tonsil cell cultures (91% inhibition at 10⁻⁵ M)[3] In vitro studies have characterized the biological activity of hydrocortisone hemisuccinate using various cell culture systems. The compound inhibits the biological activities of IL-6 and IL-3 with IC50 values of 6.7 μM and 21.4 μM, respectively, as demonstrated in cytokine-dependent cell line assays. In lymphocyte proliferation assays, hydrocortisone hemisuccinate (0.12-60 μM; 72 hours) suppresses the response of T lymphocytes and peripheral lymphocyte cultures to phytohemagglutinin (PHA) stimulation. The compound has been evaluated in continuous cultures of GMK (green monkey kidney) cells to determine cytotoxic doses and assess morphological changes in cellular structures. Importantly, hydrocortisone hemisuccinate has been shown to have no deleterious effect on IL-6-independent MH60 cells, indicating that its suppressive effects are specific to cytokine-dependent pathways rather than general cytotoxicity. |
| ln Vivo |
In mice, oral administration of hydrocortisone hemisuccinate (30 mg/kg) twice a day for five days results in decreased weight loss and increased food intake [2].
Loaded in pH-sensitive hydrogel significantly reduced colitis symptoms in mice (DAI score 1.8 vs. 4.2 in control)[2] In vivo studies have demonstrated the biological effects of hydrocortisone hemisuccinate across multiple animal models. In a study using opossum (Didelphis albiventris) fetuses, daily subcutaneous injections of hydrocortisone hemisuccinate (0.4 mg/15.0 g body weight) for 7 days induced significant morphological changes in intestinal microvilli. Treated animals showed microvillus length increases of over 50% in the duodenum and over 30% in the ileum compared to controls, with corresponding volume increases of approximately 65% and 33%, respectively. These changes indicate improvement in the absorptive function of the intestinal epithelium, consistent with the compound's role in promoting intestinal maturation and closure. In human studies, hydrocortisone hemisuccinate has been shown to be orally bioactive as a steroidal anti-inflammatory agent (SAID) and has been investigated for the treatment of ulcerative colitis (UC). The compound's ability to suppress pro-inflammatory cytokine activity underlies its therapeutic efficacy in inflammatory conditions. |
| Enzyme Assay |
The primary non-cellular method for characterizing the receptor interaction of hydrocortisone hemisuccinate is the glucocorticoid receptor (GR) competitive binding assay. In this cell-free procedure, cytosolic glucocorticoid receptors are isolated from target tissues such as rat liver or thymus through homogenization and ultracentrifugation. The receptor preparation is incubated with a radiolabeled high-affinity glucocorticoid ligand, typically [³H]dexamethasone or [³H]hydrocortisone, in the presence of varying concentrations of unlabeled hydrocortisone hemisuccinate. Incubation is carried out at 4°C for 12-24 hours to achieve equilibrium while minimizing ligand degradation. Separation of bound radioligand from free ligand can be achieved using validated methods including hydroxylapatite adsorption, dextran-coated charcoal (DCC) absorption, or rapid vacuum filtration through glass fiber filters (e.g., GF/B filters). The bound radioactivity retained is quantified by liquid scintillation counting. The ability of hydrocortisone hemisuccinate to displace the radiolabeled ligand is directly proportional to the reduction in radioactive signal, allowing calculation of the half-maximal inhibitory concentration (IC50) and inhibition constant (Ki). The structure-activity relationship can be further analyzed using purified recombinant GR protein and fluorescence polarization-based competitive binding assays.
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| Cell Assay |
IL-6 bioactivity assay: MH60.BSF2 cells cultured with IL-6 and test compounds for 44h. Cell viability measured via MTT assay. Hydrocortisone hemisuccinate dissolved in ethanol and diluted in medium[1]
Lymphocyte suppression: Human tonsil cells cultured with phytohemagglutinin for 72h. Hydrocortisone hemisuccinate added at initiation. Proliferation assessed via ³H-thymidine incorporation[3] A validated in vitro cell-based assay for evaluating hydrocortisone hemisuccinate's biological activity utilizes lymphocyte proliferation assays. In this protocol, peripheral blood mononuclear cells (PBMCs) are isolated from healthy donors by density gradient centrifugation. Cells are seeded into 96-well plates at a density of approximately 1-2 × 10⁵ cells per well in RPMI-1640 medium supplemented with 10% fetal bovine serum. Hydrocortisone hemisuccinate is added at varying concentrations (typically 0.12-60 μM) either simultaneously with or prior to the addition of the mitogen phytohemagglutinin (PHA) at a concentration of 5-10 μg/mL. The plates are incubated at 37°C in a humidified atmosphere of 5% CO₂ for 72 hours. Cell proliferation is assessed by adding MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) or [³H]-thymidine incorporation during the final 6-18 hours of culture. For cytokine inhibition assays, using IL-6-dependent cell lines (e.g., MH60 cells), cells are cultured in the presence of IL-6 and varying concentrations of hydrocortisone hemisuccinate for 48-72 hours. Cell viability is measured by MTT or a similar colorimetric assay. The concentration causing 50% inhibition of cytokine-induced proliferation (IC50) is determined by curve fitting (for IL-6: IC50 = 6.7 μM). |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (200-220 g, 10-11 weeks) induced colitis [2]
Doses: 30 mg/kg Route of Administration: Po twice (two times) daily for 5 days Experimental Results: Significant reduction in disease Activity index (DAI) scores and myeloperoxidase (MPO) activity compared with the 2,4,6-trinitrobenzene sulfonic acid (TNBS) group. Weight gain. Colitis treatment: Hydrocortisone hemisuccinate loaded in hydrogel (drug content 15% w/w). Administered rectally (100 mg/kg) to DSS-induced colitis mice daily for 7 days[2] A representative in vivo protocol for studying hydrocortisone hemisuccinate uses the opossum fetal model to assess intestinal maturation. In this procedure, pregnant opossums (Didelphis albiventris) are housed under standard conditions. Fetuses with crown-rump lengths of 45-55 mm are identified. The treatment group (n=41 fetuses) receives daily subcutaneous injections of hydrocortisone hemisuccinate at a dose of 0.4 mg per 15.0 g body weight for 7 consecutive days. The control group (n=20 fetuses) receives vehicle injections only. Seven days after the first injection, animals are euthanized, and tissue fragments from the duodenum and ileum are collected. Samples are prepared for transmission electron microscopy (TEM) examination by fixation in glutaraldehyde, post-fixation in osmium tetroxide, dehydration through graded alcohols, and embedding in epoxy resin. Ultrathin sections (60-90 nm) are cut, stained with uranyl acetate and lead citrate, and examined at a final magnification of 100,000×. Microvillus lengths and widths are measured from micrographs. Microvillus volume is calculated as the volume of a cylinder (V = πr²h). Statistical comparisons between treatment and control groups are performed using appropriate tests (Student's t-test or Mann-Whitney U test). For ulcerative colitis studies, oral administration of hydrocortisone hemisuccinate in mouse models has been employed to assess therapeutic efficacy. |
| ADME/Pharmacokinetics |
The colon-targeting hydrogel showed a drug release rate of less than 10% at pH 1.2 (stomach) and more than 80% at pH 7.4 (colon) [2]
The pharmacokinetic properties of hydrocortisone hemisuccinate have been characterized primarily in human studies following intravenous administration. In a study involving 6 healthy volunteers who received 100 mg intravenous doses, the metabolism of hydrocortisone hemisuccinate was investigated. The compound is rapidly hydrolyzed in vivo to free hydrocortisone, which then undergoes typical corticosteroid metabolism. Urinary metabolites were separated into free, glucuronide, sulfate, and "unhydrolyzed" fractions. Glucuronide conjugates constituted the largest fraction of Porter-Silber (P-S) positive metabolites in 24-hour urine. The free/glucuronide ratio of P-S positive metabolites decreased progressively or remained low throughout the collection periods, indicating efficient conjugation and elimination. For all steroids studied, the INH/P-S ratio was high in the free fraction and low in the glucuronide fraction. The consistent presence of "unhydrolyzed" metabolites suggests that portions of the ester can be excreted unchanged in the urine. For water-soluble esters like hydrocortisone hemisuccinate, intravenous administration produces rapid onset of action, while oral administration is associated with variable absorption but demonstrable bioactivity. Tissue distribution studies in animal models have confirmed the compound's ability to reach target organs including the intestinal epithelium and other glucocorticoid-responsive tissues. |
| Toxicity/Toxicokinetics |
Compared with mucosal atrophy induced by free drugs, no obvious histological damage was observed in the colonic tissue [2]
The toxicological profile of hydrocortisone hemisuccinate has been evaluated through preclinical studies and clinical use. According to safety data sheets, the compound is classified as toxic, containing a pharmaceutically active ingredient, and should be handled only by personnel trained in handling potent active pharmaceutical ingredients. It is considered a moderate to severe irritant to the skin and eyes. The material safety data sheet indicates potential reproductive toxicity risks: R62 (possible risk of impaired fertility) and R63 (possible risk of harm to the unborn child). Other risk phrases include R28 (very toxic if swallowed), R38 (irritating to skin), R41 (risk of serious damage to eyes), and R48 (toxic; danger of serious damage to health by prolonged exposure). However, the National Toxicology Program (NTP), International Agency for Research on Cancer (IARC), OSHA, and ACGIH do not classify hydrocortisone hemisuccinate as a carcinogen. In vitro cell culture studies using GMK cells have been employed to determine cytotoxic doses and assess morphological changes. Long-term systemic use of hydrocortisone hemisuccinate, as with any potent glucocorticoid, carries risks of hypothalamic-pituitary-adrenal (HPA) axis suppression, immunosuppression, osteoporosis, hyperglycemia, and fluid and electrolyte disturbances. Standard laboratory safety precautions including chemical safety goggles, chemical-resistant gloves, and impervious clothing are recommended when handling this compound. |
| References |
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| Additional Infomation |
Hydrocortisone succinate is a derivative of succinic acid, in which one of its carboxyl groups is esterified with the C-21 hydroxyl group of cortisol (hydrocortisone). It is a dicarboxylic acid monoester, hemisuccinate, and tertiary α-hydroxy ketone. Its function is related to cortisol. Hydrocortisone sodium succinate is the sodium salt of hydrocortisone succinate and possesses glucocorticoid properties. The chemical structure of hydrocortisone sodium succinate is similar to that of endogenous hormones, stimulating anti-inflammatory and immunosuppressive activity, and exhibiting mild mineralocorticoid activity. The drug binds to intracellular glucocorticoid receptors and translocates to the cell nucleus, where it initiates the transcription of glucocorticoid-responsive genes (such as various cytokines and lipocortin). Lipocortin inhibits phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and inhibiting the synthesis of prostaglandins and leukotrienes, both potent inflammatory mediators. Hydrocortisone hemisuccinate is the synthetic hemisuccinate form of hydrocortisone, a corticosteroid with anti-inflammatory and immunosuppressive effects. Hydrocortisone acetate first binds to cytoplasmic glucocorticoid receptors; then, the receptor-ligand complex translocates to the nucleus, where it initiates transcription of genes encoding anti-inflammatory mediators such as cytokines and lipocortin. Lipocorticoids inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and inhibiting the synthesis of prostaglandins and leukotrienes.
Structural modifications improve water solubility, superior to hydrocortisone[2] In vitro immunosuppressive efficacy is lower than dexamethasone[3] |
| Molecular Formula |
C25H34O8
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|---|---|
| Molecular Weight |
462.54
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| Exact Mass |
462.225
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| Elemental Analysis |
C, 64.92; H, 7.41; O, 27.67
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| CAS # |
2203-97-6
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| Related CAS # |
Hydrocortisone acetate;50-03-3;Hydrocortisone;50-23-7;Hydrocortisone phosphate;3863-59-0;Hydrocortisone hemisuccinate sodium;125-04-2; 83784-20-7
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| PubChem CID |
16623
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
685.5±55.0 °C at 760 mmHg
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| Flash Point |
231.1±25.0 °C
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| Vapour Pressure |
0.0±4.8 mmHg at 25°C
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| Index of Refraction |
1.587
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| LogP |
2.13
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
908
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)COC(=O)CCC(=O)O)O)C)O
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| InChi Key |
VWQWXZAWFPZJDA-CGVGKPPMSA-N
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| InChi Code |
InChI=1S/C25H34O8/c1-23-9-7-15(26)11-14(23)3-4-16-17-8-10-25(32,24(17,2)12-18(27)22(16)23)19(28)13-33-21(31)6-5-20(29)30/h11,16-18,22,27,32H,3-10,12-13H2,1-2H3,(H,29,30)/t16-,17-,18-,22+,23-,24-,25-/m0/s1
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| Chemical Name |
4-[2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-4-oxobutanoic acid
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| Synonyms |
Oralsome; Cortisol succinate; 2203-97-6; Hydrocortisone succinate; Hydrocortisone hydrogen succinate; ORISTAR HCSHS; CHEBI:31677; Hydroxycortisone succinate; NSC-7576; Hydrocortisone hemisuccinate anhydrous
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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) |
DMSO : ~250 mg/mL (~540.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.50 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1620 mL | 10.8099 mL | 21.6198 mL | |
| 5 mM | 0.4324 mL | 2.1620 mL | 4.3240 mL | |
| 10 mM | 0.2162 mL | 1.0810 mL | 2.1620 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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