β-Aminopropionitrile   中文名称: β-氨基丙腈

β-氨基丙腈 (BAPN) 可增强体外胰岛素抵抗模型中的葡萄糖吸收，并使 GLUT4 和脂联素的表达正常化 [1]。 β-氨基丙腈（500 μM；72 h）可抑制体外宫颈癌细胞的侵袭和迁移，同时抑制缺氧诱导的 EMT 形态和标志蛋白变化[2]。

在饮食引起的肥胖大鼠中，β-氨基丙腈 (BAPN)（100 毫克/公斤/天；口服；6 周）可改善代谢状况并减少体重增加[1]。 C57BL/6 小鼠给予 β-氨基丙腈单富马酸盐（1 g/kg/天；口服；4 周）以诱导胸主动脉夹层[3]。

蛋白质印迹分析[1]
细胞类型： 3T3-L1 脂肪细胞
测试浓度： 200 μM，含 1.15 nM 和 2.87 nM TNFα
孵育时间：72 小时
实验结果：TNFα 降低了这些细胞中 GLUT4 和脂联素的表达，并增加了 SOCS3 蛋白水平。这些影响都被阻止了。细胞侵袭测定[2]
细胞类型： HeLa 和 SiHa 细胞
测试浓度： 500 μM
孵育时间： 72 小时
实验结果：两种细胞模型中缺氧引起的细胞侵袭均显着减少。

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细胞迁移测定 [2]
细胞类型： HeLa 和 SiHa 细胞
测试浓度： 500 μM
孵育时间： 72 小时
实验结果： HeLa 和 SiHa 细胞中缺氧诱导的迁移分别从 180% 和 240% 减少到 60% 和 70%。

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蛋白质印迹分析[2]
细胞类型： HeLa 和 SiHa 细胞
测试浓度： 500 μM
孵育时间：72小时
实验结果：有效阻止缺氧引起的E-cadherin下调，并强烈抑制缺氧引起的α-SMA和vimentin上调。

Animal/Disease Models: Male Wistar rats of 150 g, high-fat diet (HFD) model[1]
Doses: 100 mg/kg/day
Route of Administration: In the drinking water, 6 weeks
Experimental Results: Dramatically prevented the rise in body weight in HFD rats, but not in animals that were fed a standard diet. decreased the increase in the weight of white adipose tissue (both epididymal and lumbar) in obese animals and attenuated their enhanced adiposity. Improved fasted glucose and insulin levels and consequently decreased HOMA index in the HFD group. Improved insulin signaling in adipose tissue from obese animals.

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Animal/Disease Models: C57BL/6 mice[3]
Doses: 1 g/kg/day
Route of Administration: In the drinking water, 4 weeks
Experimental Results: Induce thoracic aortic dissection (TAD) in all mice with 24 h of Ang II infusion. Caused 87% of C57BL/6 mice to develop TAD without Ang II.

Absorption, Distribution and Excretion
BETA-AMINOPROPIONITRILE (BAPN) WAS FOUND IN URINE WITHIN 1 HR OF ORAL ADMIN. ORAL 250 MG BAPN AT 6 HR INTERVALS EACH DAY FOR 21 DAYS RESULTED IN URINARY BAPN RECOVERIES APPROXIMATING 16% OF TOTAL DOSE. BAPN WAS NOT DETECTED IN SPECIMENS COLLECTED LATER THAN 7 HR AFTER CESSATION OF BAPN DOSAGE. URINARY CYANOACETIC ACID APPEARED MORE SLOWLY THAN BAPN & INCR GRADUALLY TO APPROX 3 TIMES THAT OF URINARY BAPN. AFTER BAPN WAS DISCONTINUED, THERE WAS PROLONGED URINARY EXCRETION OF BAPN-DERIVED CYANOACETIC ACID.
AFTER APPLICATION TO THE SKIN OF RATS, (14)C-BAPN FREE BASE WAS ABSORBED MORE RAPIDLY AND TO A GREATER EXTENT THAN THE FUMARATE SALT. SIX HOURS AFTER TOPICAL ADMINISTRATION OF THE FREE BASE ONLY TRACES OF (14)C WERE FOUND ON THE SKIN AND LESS THAN 1% OF THE DOSE WITHIN THE SKIN SECTION SUGGESTING RAPID DRUG ABSORPTION.

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Metabolism / Metabolites
...BETA-AMINOPROPIONITRILE /IS METABOLIZED/ INTO CYANOACETIC ACID...
BETA-AMINOPROPIONITRILE (BAPN) WAS FOUND IN URINE WITHIN 1 HR OF ORAL ADMIN. ORAL 250 MG BAPN AT 6 HR INTERVALS EACH DAY FOR 21 DAYS RESULTED IN URINARY BAPN RECOVERIES APPROXIMATING 16% OF TOTAL DOSE. BAPN WAS NOT DETECTED IN SPECIMENS COLLECTED LATER THAN 7 HR AFTER CESSATION OF BAPN DOSAGE. URINARY CYANOACETIC ACID APPEARED MORE SLOWLY THAN BAPN & INCR GRADUALLY TO APPROX 3 TIMES THAT OF URINARY BAPN. AFTER BAPN WAS DISCONTINUED, THERE WAS PROLONGED URINARY EXCRETION OF BAPN-DERIVED CYANOACETIC ACID.
Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)

Toxicity Summary
Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

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Interactions
USE OF BAPN (1 G/KG/DAY) FOR PERIOD OF 8 WK CAUSED SIMULTANEOUS CHANGES IN SKIN & AORTIC CONNECTIVE TISSUES OF RATS. IN SKIN, COLLAGEN TISSUE WAS DISLOCATED & BROKEN INTO FRAGMENTS, ELASTIC TISSUE DISAPPEARED & FIBROBLASTS WERE VACUOLIZED. ADDITION OF PYRIDINOL CARBAMATE (PDC) TO BAPN PREVENTS FORMATION OF LESIONS OF ELASTIC TISSUE & OF FIBROBLASTS. WHEN GIVEN AFTER CESSATION OF LATHYROGEN TREATMENT, PDC ARRESTED FORMATION OF LESIONS & ACCELERATED THEIR REGRESSION.
A DOSE OF 2,500 MG/KG BAPN GIVEN BY GAVAGE ON DAY 11 TO PREGNANT HAMSTERS PRODUCED 69.5% SKELETAL ANOMALIES IN THE OFFSPRING. ADMINISTRATION OF BETA-HYDROXYETHYLRUTOSIDES (WHICH PROTECT AGAINST COLLAGEN DAMAGE FROM LATHYROGENS) IMMEDIATELY AFTER BAPN TO THE PREGNANT ANIMALS RESULTED IN SIGNIFICANTLY DECREASED TERATOGENIC RESPONSE. THIS SUPPORTS THE VIEW THAT THE MECHANISM FOR BAPN-INDUCED SKELETAL DYSMORPHOGENESIS IS THE INHIBITION OF CROSS-LINKING DURING THE MATURATION OF COLLAGEN FIBERS.

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Non-Human Toxicity Values
LD50 Mouse ip 1152 mg/kg

[1]. Miana M, et al. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats. Dis Model Mech. 2015 Jun;8(6):543-51.
[2]. Yang X, et al. Inactivation of lysyl oxidase by β-aminopropionitrile inhibits hypoxia-induced invasion and migration of cervical cancer cells. Oncol Rep. 2013 Feb;29(2):541-8.
[3]. Ren W, et al. β-Aminopropionitrile monofumarate induces thoracic aortic dissection in C57BL/6 mice. Sci Rep. 2016 Jun 22;6:28149.

Beta-aminopropionitrile is an aminopropionitrile carrying an amino group at the beta-position. It has a role as a plant metabolite, an antineoplastic agent, an antirheumatic drug and a collagen cross-linking inhibitor. It is a conjugate base of a beta-ammoniopropionitrile.
beta-Aminopropionitrile is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
3-Aminopropanenitrile has been reported in Euglena gracilis with data available.
beta-Aminopropionitrile is a toxic amino-acid derivative. On an unusual case of the Cantrell-sequence in a premature infant with associated dysmelia, aplasia of the right kidney, cerebellar hypoplasia and circumscribed aplasia of the cutis, maternal history suggested an occupational exposure to aminopropionitriles prior to pregnancy. The characteristic features of the Cantrell-sequence--anterior thoraco-abdominal wall defect with ectopia cordis and diaphragm, sternum, pericardium, and heart defects--have been observed in animals following maternal administration of beta-aminopropionitrile. Some species of lathyrus (chickling pea, Lathyrus sativus- related), notably Lathyrus odoratus, are unable to induce human lathyrism but contain beta-aminopropionitrile, that induces pathological changes in bone (osteolathyrism) and blood vessels (angiolathyrism) of experimental animals without damaging the nervous system. The administration of beta-aminopropionitrile has been proposed for pharmacological control of unwanted scar tissue in human beings. beta-Aminopropionitrile is a reagent used as an intermediate in the manufacture of beta-alanine and pantothenic acid. (A11439, A11440, A11441)
Reagent used as an intermediate in the manufacture of beta-alanine and pantothenic acid.
See also: ... View More ...

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Mechanism of Action
The mechanism of the effect is unknown, but it is thought to be by some action on growth of certain mesodermal tissues. It is not due to one of its major metabolites, cyanoacetic acid, and both the free amino group and the cyano group seem essential for activity. It is not produced if the amino group is in the alpha position, or if in the gamma position in butyronitrile.
IT HAS BEEN SUGGESTED THAT LATHYROGENIC AGENTS ACT BY BLOCKING CERTAIN CARBONYL GROUPS NORMALLY PRESENT IN COLLAGEN, & THUS INTERFERING WITH FORMATION OF CROSS LINKAGES. THEIR ACTION MAY BE RETARDED BY RESERPINE OR BY CALCIUM SALTS. /LATHYROGENIC AGENTS/

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Therapeutic Uses
EXPTL USE: ADMIN OF LYSYL OXIDASE INHIBITOR, BAPN, PREVENTED DEVELOPMENT OF HYPERTENSION & DECR AMT OF VASCULAR COLLAGEN IN RATS IN WHICH HYPERTENSION HAD BEEN INDUCED. HISTOLOGICAL EXAM REVEALED THAT ARTERIOSCLEROTIC CHANGES WERE PREVENTED BY BAPN.
EXPTL USE: IN YOUNG HYPERTENSIVE RATS, BAPN (20 MG, IP DAILY, FOR 2 WK) PREVENTED DEVELOPMENT OF HYPERTENSION. IN ADULT SPONTANEOUS HYPERTENSIVE RATS (50 MG, IP, DAILY FOR 2 WK) DECR BLOOD PRESSURE.
EXPTL USE: RATS WITH SC IMPLANTED POLYVINYL ALCOHOL SPONGES AND WITH INFLICTED SKIN INCISION WOUNDS RECEIVED A SINGLE INJECTION OF BETA-AMINOPROPIONITRILE (BAPN) AT 4 DOSAGES RANGING FROM 1-40 MG/100 G. EVEN THE LOWEST DOSE OF BAPN INHIBITED LYSYL OXIDASE ACTIVITY FOR 6 HOURS; WITH LARGER DOSAGES THE INHIBITION LASTED LONGER, AT 40 MG BAPN, AT LEAST 48 HOURS. THE MAGNITUDE AND DURATION OF INHIBITION WERE REFLECTED IN THE EXTRACTABILITY OF COLLAGEN AND BURSTING STRENGTH OF THE WOUND. THE DATA SUGGEST THAT A MINIMAL DOSE OF BAPN WOULD BE CLINICALLY EFFECTIVE IF EITHER THE METABOLISM OF THE DRUG WERE REDUCED (BY MONOAMINE OXIDASE INHIBITORS) OR A SUSTAINED-RELEASE PREPARATION OF BAPN WERE USED.
EXPTL USE: BETA-AMINOPROPIONITRILE (BAPN) WAS TESTED FOR ABILITY TO PREVENT EXCESS COLLAGEN FORMATION IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN THE HAMSTER. TWO GROUPS RECEIVED 1 ENDOTRACHEAL DOSE OF BLEOMYCIN; ONE OF THESE WAS INJECTED WITH BAPN TWICE DAILY FOR 30 DAYS. A 3RD GROUP RECEIVED SALINE AND BAPN. THE BLEOMYCIN INCREASED COLLAGEN CONTENT, DECREASED LUNG VOLUME, AND PRODUCED FIBROSIS AND A MORTALITY RATE OF 51%. ADMINISTRATION OF BAPN TO BLEOMYCIN-TREATED ANIMALS PREVENTED EXCESS COLLAGEN ACCUMULATION, PRODUCED LESS FIBROSIS, AND LESSENED MORTALITY RATE TO 24%; BAPN ALONE HAD NO EFFECT ON LUNG MECHANICS OR COLLAGEN CONTENT.

C₃H₆N₂

70.09

70.053

151-18-8

1647

Liquid

0.9±0.1 g/cm3

186.3±13.0 °C at 760 mmHg

< 25 °C

66.5±19.8 °C

0.7±0.4 mmHg at 25°C

1.430

-1.02

49.81

1

2

1

5

49.2

0

C(CN)C#N

AGSPXMVUFBBBMO-UHFFFAOYSA-N

InChI=1S/C3H6N2/c4-2-1-3-5/h1-2,4H2

3-aminopropanenitrile

βAminopropionitrile; β Aminopropionitrile

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 本产品在运输和储存过程中需避光。  (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

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

DMSO : ~100 mg/mL (~1426.74 mM)
H2O : ~50 mg/mL (~713.37 mM)

配方 1 中的溶解度: ≥ 3.25 mg/mL (46.37 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 32.5 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 3.25 mg/mL (46.37 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 32.5 mg/mL 澄清 DMSO 储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 3.25 mg/mL (46.37 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 32.5 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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配方 4 中的溶解度: 100 mg/mL (1426.74 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。