calcium;4-oxopentanoate | 591-64-0

• 物质功能分类: 原料药 - 水、电解质及酸碱平衡调节药 - 电解质平衡调节药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: calcium;4-oxopentanoate
• 英文别名: Levulinic Acid Calcium Salt
• CAS: 591-64-0
• 化学式: C₁₀H₁₄CaO₆
• 分子量: 270.29
• InChiKey: APKDPOQXVKRLEP-UHFFFAOYSA-L

物化性质

• 熔点：
  123 °C
• LogP：
  -0.490 (est)
• 稳定性/保质期：
  基本性质：这种物质带有轻微的焦糖气味，味道略带苦咸。在常压下的室温和干燥条件下会失去一分子结晶水；当温度达到50℃时，所有结晶水将完全消失。

计算性质

• 辛醇/水分配系数(LogP)：
  -2.17
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  6

ADMET

代谢

尽管钙乙酰丙酸一旦进入体内就会解离成可吸收的钙离子，但已有研究表明，乙酰丙酸成分会被代谢为4-羟基戊酸——一种具有与“约会强奸药”γ-羟基丁酸类似的药理效果但在效力上较低的化合物。

Although calcium levulinate dissociates into absorbable calcium ion once it is administered into the body, there have been studies to suggest that the levulinate component is metabolized to 4-hydroxypentanoate - a compound that has similar pharmacologic effects as but at a lower level of potency than the 'date rape' drug gamma-hydroxybutyrate.

来源:DrugBank

毒理性

• 蛋白质结合

关于左旋乳酸钙蛋白结合的现成数据并不容易获得，尽管存在许多不同的钙结合蛋白，它们在不同的细胞和组织中分布，并参与特定的生物学功能。这些蛋白包括钙调蛋白、肌钙蛋白C、钙视网膜蛋白和钙神经素等。

Readily accessible data regarding the protein binding of calcium levulinate is not available, although many different calcium-binding proteins exist, with different cellular and tissue distribution and involvement in specific biological function. Some of these proteins include calmodulin, calsequestrin, calretinin, and calcineurin, among others.

来源:DrugBank

吸收、分配和排泄

• 吸收

普通钙的吸收主要发生在十二指肠，通过一种活跃的跨细胞和可饱和系统，该系统受1,25(OH)2D的刺激和调节，以及通过在小肠的空肠和回肠，甚至在大肠中的一种被动的、独立于维生素D的细胞旁运输进行，即使在大剂量摄入时，大肠的吸收也只有大约4%。最终，钙的吸收主要取决于摄入量 - 通常情况下，摄入量较低时吸收增加，摄入量高时吸收减少。尽管认为钙乙酰丙酸酯的配方是一种易于通过肠壁吸收的低分子量有机钙离子型，但关于其特定吸收的数据并不容易获得。

General calcium absorption occurs primarily in the duodenum by an active transcellular and saturable system, which is stimulated and regulated by 1,25(OH)2D,25 and through a passive and vitamin D-independent paracellular transport in the jejunum and ileum, and even in the colon - where absorption is only about 4% even when the intake is high. Ultimately, calcium absorption depends mainly on the amount of intake - in general, absorption increases at lower intakes and decreases at high intakes. Readily accessible data regarding the specific absorption of calcium levulinate is not available although the formulation is considered a low molecular weight organic calcium ion type that is easily absorbed through the intestinal wall.

来源:DrugBank

吸收、分配和排泄

• 消除途径

钙主要通过尿液和粪便排出体外，也会通过其他身体组织和液体，比如汗液排出。总体而言，一个健康的成年男女通过肾脏排出的典型每日钙流失量大约是5毫摩尔/天，而内源性粪便钙流失量在成年人中约为每天2.1毫克/千克，在儿童中约为每天1.4毫克/千克。

Calcium leaves the body mainly in urine and feces, but also in other body tissues and fluids, like sweat. Overall, a typical daily calcium loss for a healthy adult man or woman via renal excretion is approximately 5 mmol/day while endogenous fecal calcium losses are about 2.1 mg/kg per day in adults and about 1.4 mg/kg per day in children.

来源:DrugBank

吸收、分配和排泄

• 分布容积

99%的钙储存在骨骼和牙齿中，以支持其结构和功能。在其他地方，1%或更少的钙用于基本代谢功能，如血管收缩和扩张、肌肉功能、神经传递、细胞内信号传导和激素分泌等活动。

99% of the body's calcium supply is stored in the bones and teeth where it supports their structure and function. Elsewhere, 1% or less of this calcium supply is used for essential metabolic functions like vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling, and hormonal secretion, among other activities.

来源:DrugBank

吸收、分配和排泄

• 清除

尽管存在个体间的差异，一般的临床实验室检查会列出一些参考钙清除值，被认为是“正常范围”，比如尿液钙大约小于250毫克/24小时。

Despite inter-individual differences, general clinical lab tests list some reference calcium clearance values as being considered a 'normal range', like urine calcium as approximately < 250 mg/24 h.

来源:DrugBank

安全信息

• WGK Germany：
  3
• 储存条件：
  贮存： 将密器密封，并储存在密封的主要容器中。应将其放置在阴凉、干燥处。

SDS

Calcium Levulinate Dihydrate Revision number: 5
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: Calcium Levulinate Dihydrate

Revision number: 5

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Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
Not classified
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS Not classified
GHS label elements, including precautionary statements
Pictograms or hazard symbols None
No signal word
Signal word
Hazard statements None
None
Precautionary statements:

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
Components: Calcium Levulinate Dihydrate
Percent: >98.0%(T)
CAS Number: 591-64-0
Synonyms: 3-Acetylpropionic Acid Calcium Salt , Levulinic Acid Calcium Salt , 4-Oxovaleric Acid
Calcium Salt
C10H14CaO6·2H2O
Chemical Formula:

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Section 4. FIRST AID MEASURES
Inhalation: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Get medical advice/attention if you feel unwell.
Skin contact: Remove/Take off immediately all contaminated clothing. Rinse skin with
water/shower. If skin irritation or rash occurs: Get medical advice/attention.
Eye contact: Rinse cautiously with water for several minutes. Remove contact lenses, if present
and easy to do. Continue rinsing. If eye irritation persists: Get medical
advice/attention.
Ingestion: Get medical advice/attention if you feel unwell. Rinse mouth.
A rescuer should wear personal protective equipment, such as rubber gloves and air-
Protection of first-aiders:
tight goggles.

---

Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide.
media:
Calcium Levulinate Dihydrate

---

Section 5. FIRE-FIGHTING MEASURES
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
Special protective When extinguishing fire, be sure to wear personal protective equipment.
equipment for firefighters:

---

Section 6. ACCIDENTAL RELEASE MEASURES
Use personal protective equipment. Keep people away from and upwind of spill/leak.
Personal precautions,
protective equipment and Entry to non-involved personnel should be controlled around the leakage area by
emergency procedures: roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

---

Section 7. HANDLING AND STORAGE
Precautions for safe handling
Handling is performed in a well ventilated place. Wear suitable protective equipment.
Technical measures:
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a local exhaust if dust or aerosol will be generated.
Advice on safe handling: Avoid contact with skin, eyes and clothing.
Conditions for safe storage, including any
incompatibilities
Storage conditions: Keep container tightly closed. Store in a cool and dark place.
Store away from incompatible materials such as oxidizing agents.
Packaging material: Comply with laws.

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Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Install a closed system or local exhaust as possible so that workers should not be
Engineering controls:
exposed directly. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator. Follow local and national regulations.
Hand protection: Protective gloves.
Eye protection: Safety glasses. A face-shield, if the situation requires.
Skin and body protection: Protective clothing. Protective boots, if the situation requires.

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Physical state (20°C): Solid
Form: Crystal- Powder
Colour: White - Very pale yellow
Odour: No data available
pH: No data available
Melting point/freezing point:123°C
No data available
Boiling point/range:
Flash point: No data available
Flammability or explosive
limits:
No data available
Lower:
Upper: No data available
No data available
Relative density:
Solubility(ies):
No data available
[Water]
[Other solvents] No data available
Calcium Levulinate Dihydrate

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Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide
products:

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Section 11. TOXICOLOGICAL INFORMATION
orl-rat LD50:6140 mg/kg
Acute Toxicity:
Skin corrosion/irritation: No data available
No data available
Serious eye
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
IARC = No data available
NTP = No data available
No data available
Reproductive toxicity:
RTECS Number: SA4000000

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Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
Fish: No data available
Crustacea: No data available
Algae: No data available
Persistence / degradability: No data available
Bioaccumulative No data available
potential(BCF):
Mobility in soil
No data available
Log Pow:
Soil adsorption (Koc): No data available
Henry's Law No data available
constant(PaM3/mol):

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Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system.
Observe all federal, state and local regulations when disposing of the substance.

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Section 14. TRANSPORT INFORMATION
Does not correspond to the classification standard of the United Nations
Hazards Class:
UN-No: Not listed

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Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.
Calcium Levulinate Dihydrate

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

化学性质

该物质为白色结晶或颗粒状粉末，熔点125℃。易溶于水，微溶于醇，不溶于醚和氯仿。它具有轻微的焦糖气味，并带苦咸味，在真空室温干燥条件下会失去一分子结晶水，在50℃时所有结晶水将全部失去。

制备方法

由糠醇经重排、水解、成盐而得。

用途

用作营养药，治疗缺钙症。

反应信息

• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 生成 calcium;4-oxopentanoate
  参考文献：
  名称：

  Mustafa; Hilmy, Journal of the Chemical Society, 1947, p. 1698

  摘要：

  DOI：

文献信息

• [EN] PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF<br/>[FR] INHIBITEURS DE LA PRMT5 CONTENANT UNE DIHYDRO- OU TÉTRAHYDRO-ISOQUINOLÉINE ET LEURS UTILISATIONS
  申请人：EPIZYME INC

  公开号：WO2014100730A1

  公开（公告）日：2014-06-26

  Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.

  本文描述了式（A）的化合物，其药学上可接受的盐以及药物组合物。本发明的化合物对抑制PRMT5活性是有用的。还描述了利用这些化合物治疗PRMT5介导的疾病的方法。
• PRMT5 INHIBITORS AND USES THEREOF
  申请人：Duncan Kenneth W.

  公开号：US20190083482A1

  公开（公告）日：2019-03-21

  Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

  本文描述了式（I）的化合物，其药学上可接受的盐以及药物组合物。本发明的化合物对抑制PRMT5活性是有用的。还描述了利用这些化合物治疗PRMT5介导的疾病的方法。
• [EN] USES OF PYRIMIDOPYRIMIDINONES AS SIK INHIBITORS<br/>[FR] UTILISATIONS DE PYRIMIDOPYRIMIDINONES COMME INHIBITEURS DE SIK
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2018160774A1

  公开（公告）日：2018-09-07

  The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.

  本公开提供了一种在需要增加皮肤色素沉着的受试者中使用盐诱导激酶（SIK）抑制剂的方法，例如，本发明的公式(I)的大环化合物，公式(II)、(III)和(IV)的 bicyclic urea化合物，以及公式(V)、(VI)、(VI-A)或(VII)的化合物。还提供了包括或涉及本文所述化合物的药物组合物、方法和用途。
• [EN] IMIDAZOLYL KINASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'IMIDAZOLYL KINASE ET LEURS UTILISATIONS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2016014542A1

  公开（公告）日：2016-01-28

  The present disclosure provides imidazolyl compounds of Formula (I) and methods of preparing the compounds. The provided compounds are able to bind protein kinases and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase in a subject or cell and/or in treating or preventing a disease (e.g., proliferative disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

  本公开提供了公式(I)的咪唑啉化合物及其制备方法。所提供的化合物能够结合蛋白激酶，并且可能在调节（例如，抑制）主体或细胞中的蛋白激酶活性以及/或在需要治疗的主体中治疗或预防疾病（例如，增殖性疾病、遗传性疾病、血液病、神经病、疼痛状况、精神障碍或代谢障碍）方面有用。此外，还提供了包括或涉及本文所述化合物的药物组合物、试剂盒、方法和用途。
• [EN] CORTISTATIN ANALOGUES AND SYNTHESES AND USES THEREOF<br/>[FR] ANALOGUES DE CORTISTATINE ET SYNTHÈSES ET UTILISATIONS ASSOCIÉES
  申请人：HARVARD COLLEGE

  公开号：WO2015100420A1

  公开（公告）日：2015-07-02

  Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the β-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGFβ/BMP pathway, methods of modulating HIF-1 -alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

  本文提供了公式（A）、（B）、（C）、（D）和（E）的化合物、药用可接受的盐、季铵盐和N-氧化物，以及它们的药物组合物。公式（A）、（B）、（C）、（D）和（E）的化合物被认为是有用的治疗剂，用于治疗各种疾病，例如，包括但不限于，与血管生成和与CDK8和/或CDK19激酶活性相关的疾病。还提供了抑制CDK8和/或CDK19激酶活性的方法，调节β-连环蛋白途径的方法，调节STAT1活性的方法，调节TGFβ/BMP途径的方法，调节细胞中HIF-1α活性的方法，以及使用公式（A）、（B）、（C）、（D）或（E）的化合物增加BIM表达以诱导凋亡的方法。还提供了CDK8和CDK19点突变体及其使用方法。

表征谱图