Some of the most deadly animals on earth are poisonous. Venom is their deadly weapon, used for self-defense or attack. After the toxin is injected into the skin, it becomes venom. There are hundreds of deadly hypodermic syringes in nature. But it has a long history for human beings to transform some of the most toxic substances on the earth into useful and even life-saving drugs. For example, Botox, Botox, can kill one million people in 1g. However, by paralyzing facial muscles, it can remove some wrinkles.

However, its effect is not limited to this. In fact, Botox was first used in the eyes The treatment of family diseases, such as crossed eyes and eyelid twitch, is also used to prevent migraine, which is just one of the many terrible substances that have been fully utilized. Scientists are more and more turning the most lethal substances in the animal kingdom into drugs. With only a small amount, they can have good therapeutic effect. In other words, they are very ideal drugs. The molecular weight of animal toxin polypeptide is relatively small compared with other toxins, and it has high specificity and molecular diversity.

It is directly encoded by genes, with small dosage but strong toxicity. It is the key physiological component that acts on the target organism. Therefore, as a natural resource of drug research and development, animal toxin polypeptides are highly valued. A large number of drugs derived from animal toxin polypeptides have been approved by FDA, and some polypeptides derived from animal toxins are in clinical trials.1. Snake toxin polypeptide drugs

Snake venom is a mixture of enzyme and non enzyme protein / polypeptide. Many drugs derived from snake venom polypeptide have been used in clinical treatment.

A pentapeptide compound extracted from the venom of Bothrops jaracaca of Agkistrodon halys Pallas is the enhancer of bradykinin. The structure of the pentapeptide compound was cut and the minimal pharmacophore ala Pro dipeptide was modified.

An oral drug captopril was synthesized. Captopril can reduce blood pressure by increasing bradykinin activity and inhibiting thrombin (ACE). It is a conventional drug for the treatment of hypertension. For the structural modification of captopril, enalapril, lisinopril, ramipril, fosinopril and other drugs were successively developed.

Tirofiban, found in echiscarinatus, is a mimic of viper venom protein peptide, an antiplatelet drug, also known as glycoprotein IIb / IIIa inhibitor. Another antiplatelet drug, eptifibatide, is almost on the market at the same time as tirofiban. It is a synthetic cyclic heptapeptide, which mimics the one found in the venom of the southeast Jurassic rattlesnake (Sistrurus miliarius marbouri) and has a strong role in disintegrin. The study shows that etifeba is a little safer than Tilofiban in patients with acute coronary syndrome, but there is no significant difference in efficacy.

Ximelagatra, an oral anticoagulant from Naja naja atra, is a vitamin K antagonist, which has been approved in some European and South American countries, but has not been approved by FDA, because the increase of ALT may lead to the increase of the hepatotoxicity of the drug. As a result, the development of the compound was halted and withdrawn from the market in 2006.Cenderitide from the venom of dendroapis angusticeps is the first one to be found. It has a certain inhibition on the degradation of neutral endopeptidase. Preliminary clinical data show that cenderitide improves renal function.

A series of phase I and phase II trials have been completed in patients with heart failure treated with cenderitide, but researchers are concerned that the adverse effects of the drug may outweigh the benefits. Ketongning injection and compound ketongning (cloqu tablets), which are refined from cobratoxin extracted from short chain α - neurotoxin of cobra snake venom, have the characteristics of strong analgesic effect, long efficacy time and little addiction.

They have been used in clinical treatment for many years. Recent studies have shown that cobra neurotoxin can produce central analgesia and high analgesia through adenosine A1 and A2 receptors, and its analgesic effect is stronger than that of morphine. In addition, cardiotoxin III (also known as cytotoxin III) isolated from Naja naja atra Venom can inhibit the migration and invasion of MDA-MB-231 breast cancer cells without causing apoptosis or cell cycle arrest.

Hemocoagulase Agkistrodon is a kind of double chain snake venom thrombin (svtle), which has good hemostatic activity, safety and small side effects. It is listed as the national first-class drug (commodity name suling) in China. Phase III clinical trial shows that it has good coagulation and hemostatic function.

\1. Scorpion toxin polypeptide drugs

Scorpion is a precious resource of traditional Chinese medicine in China. Traditional Chinese medicine believes that scorpion has the functions of calming the wind, relieving spasm, dredging collaterals, relieving pain, attacking poison and dispersing the knot. It is mainly used for the diagnosis and treatment of convulsion, epilepsy, spasm, stroke, tetanus and cancer.Scorpion venom, which exists in the gland tissue of scorpion tail, has complex components, including neurotoxin, cytotoxic peptide, protease and other toxic components. It is a kind of mixture of proteins or polypeptides with various biological activities. The specific binding of these toxins to ion channels can block the channel current or change the gating dynamics, thus changing the permeability of cell membrane.

Chlorotoxin polypeptide was found in leiurus quinquestriatus venom of scorpion to delay the activity of human glioma cells in vitro. The venom of Tityus dispans, a Venezuelan scorpion, has antibacterial and antiparasitic activities and can inhibit the growth of Leishmania in vitro. Bengalin, a toxin protein of black scorpion, can induce apoptosis of human leukemic cells and improve the biochemical indexes of osteoporosis in female rats in vitro. α - neurotoxin found in scorpion venom can delay the inactivation of sodium channel at neuromuscular junction, while the inactivation of sodium channel may enhance the reflex and airway contraction of neuromuscular, which can theoretically treat sleep apnea.

\2. Anemone toxin polypeptide drugs

Anemone is one of the oldest poisonous animals in existence. Like other members of echinozoophylum, Anemone has many special cells, which are widely distributed in the whole body. SHK toxin isolated from sea anemone is an effective Kv1.3 channel blocker. Kv1.3 channel is very important in the activation of human effector memory T cells (proliferation and cytokine production). SHK can treat T cell-mediated autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. Kv1.3 receptor blocker is also considered to be the target of obesity treatment, SHK toxin has potential use in the treatment of obesity and insulin resistance.Shk-186 is an analog of SHK toxin, now known as dalazatide drug. Now it has successfully completed clinical trials and entered the drug market for the treatment of autoimmune diseases.

\3. Hirudotoxin polypeptide drugs

Leech, as an important traditional Chinese medicine, has many functions in the treatment of cerebral hemorrhage and other thrombus related diseases. Hirudin is an effective anticoagulant in the salivary glands of leeches. Hirudin can inhibit the formation of thrombus and prevent the coagulation of host blood. Pharmacology research shows that hirudin has the functions of anticoagulation, antithrombotic, anti atherosclerotic, anti platelet aggregation, anti-tumor, anti-inflammatory, improving Hemorheology and protecting cerebral ischemia-reperfusion injury.

Hirudin based anticoagulants include recombinant hirudin (lepirudin and Desirudin) and hirudin analogue bivalirudin. Lepirudin was approved by the FDA for the treatment of heparin related thrombocytopenia (HIT) and related thromboembolic diseases, but was withdrawn in 2012 for commercial reasons. Disirudin has been approved by FDA for prevention of deep vein thrombosis (DVT) or knee arthroplasty. Bivalirudin has been approved by FDA for the treatment of unstable angina after percutaneous coronary intervention (PCI), with an increased risk of hit or hit.

However, the use of these thrombin inhibitors has several disadvantages, such as bleeding, strong dependence on renal function, lack of antidotes and rebound hypercoagulability. Therefore, it is urgent to develop efficient and safe derivatives of hirudin.

Although there are still a large number of animal toxins that have not been developed, great achievements have been made in the clinical application of animal toxin polypeptide drugs, making more people realize the great potential and Prospect of the development of animal toxin polypeptide drugs. However, the effectiveness and safety of many animal toxins in clinical treatment need to be further verified, so the drug development based on animal toxins also has great challenges.

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Chengdu Shengnuo Biotechnology Co., Ltd. has "Chengdu polypeptide drug engineering technology research center" in Chengdu, mainly engaged in polypeptide, polypeptide drug and beauty peptide research. Our zero defect has passed the FDA certification, and now it has become the first-class professional peptide drug and product development, technology transfer, technical service and peptide drug industry in the scale production and export of China's parks.