NSAID; COX-1/2

Bendazac is a monocarboxylic acid that is glycolic acid in which the hydrogen attached to the 2-hydroxy group is replaced by a 1-benzyl-1H-indazol-3-yl group. Although it has anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties and has been used for the treatment of various inflammatory skin disorders, its principal effect is to inhibit the denaturation of proteins. Its lysine salt is used in the management of cataracts. It has a role as a radical scavenger and a non-steroidal anti-inflammatory drug. It is a member of indazoles and a monocarboxylic acid.

---

Bendazac is an oxyacetic acid. Despite possessing anti-inflammatory, anti-necrotic, choleretic, and anti-lipidemic characteristics, most research has revolved around studying and demonstrating the agent's principal action in inhibiting the denaturation of proteins - an effect that has primarily proven useful in managing and delaying the progression of ocular cataracts [A39863. A39863]. Bendazac, however, has since been withdrawn or discontinued in various international regions due to its capability or risk for eliciting hepatotoxicity in patients although a small handful of regions may continue to have the medication available for purchase and use either as a topical anti-inflammatory/analgesic cream or eye drop formulation.

To investigate the preventive and protective effects of Bendazac lysine (BDL) on experimental early diabetic nephropathy (DN) rats.
Results: The physical behaviors of early DN rats were hypopraxia, cachexia, and polyuria, while those treated with high doses of BDL were vibrant and vigorous. For BDL-treated DN rats, when compared with vehicle-treated DN rats, the blood glucose level and the intensity of oxidative stress were ameliorated. Also, the microalbuminuria level, AGE either in serum or in renal, and AR activity were significantly reduced. Furthermore, the expression of TGF-beta1 mRNA in the kidney cortex was declined and the thickness of glomerular base membrane was decreased significantly. The ultrastructure of glomerulus and mesangial matrix of BDL-treated DN rats were ameliorated.
Conclusion: BDL has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.[1]

---

Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats.
Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks.
Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail-flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end-products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na+/K+-ATPase in the nerves and erythrocytes.
Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ-diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN. [2] https://onlinelibrary.wiley.com/doi/10.1111/j.1440-1681.2006.04515.x

Diabetic animals and protocol [2]
Male Sprague-Dawley rats with a mean bodyweight of 200 ± 10 g were used. Diabetic rats were induced by intraperitoneal injection of 75 mg/kg STZ dissolved in 0.1 mol/L citrate buffer (pH 4.4). Three days (72 h) after STZ injection, rats with fasting blood glucose levels over 13.9 mmol/L were used in the experiments. Diabetic rats were treated with low, medium and high doses of BDL (50, 100 and 200 mg/kg, respectively). Other groups of diabetic rats were treated with EPS 50 mg/kg (EPS group) and 1% CMC (5 mL/kg) only (DPN group). Age- and weight-matched male Sprague-Dawley rats that had not been made diabetic were used as controls and were treated with 1% CMC (5 mL/kg) only (NS group). All drugs were administered by oral gavage twice a day for 12 weeks. Experimental animals were given standard pellet diet and water ad libitium, kept in the laboratory animal house under specific pathogen-free (SPF) and constant temperature (25 ± 1°C) conditions and a 12 h light–dark cycle.
Bendazac lysine (BDL) was suspended in 1% carboxymethyl cellulose (CMC) at different concentrations (1.0, 2.0 and 4.0%).

---

Induction of Diabetic nephropathy (DN) model and study protocol [1]
Diabetic rats were induced with an ip injection of 60 mg/kg of STZ (dissolved in pH 4.5 citrate buffer immediately before injection), while controlled normal standard rats (NS group, n=10) received 2.5 mL/kg of citrate buffer. Induction of the diabetic state was confirmed by measuring the blood glucose level at the 72 h after the injection of STZ. The rats whose blood glucose concentrations were ≥13.88 mmol/L were randomly allotted into 5 groups: DN rats treated with 1% CMC solution (DN group, n=10); DN rats treated with 100, 200, and 400 mg/kg of Bendazac lysine (BDL) for BL group (low dose, n=10), BM group (moderate dose, n=11), and BH group (high dose, n=10), respectively; and DN rats treated with 100 mg/ kg of epalrestat (EPS group, n=10). The same volume of CMC solution was administered to the NS group (n=10). The animals were housed in a controlled environment (24±1 °C, 12-h light: 12-h dark cycle, onset of light at 07:00 AM) and were allowed food and water ad libitum.

rat LD50 oral 3100 mg/kg BEHAVIORAL: ATAXIA; LUNGS, THORAX, OR RESPIRATION: DYSPNEA Medicamentos de Actualidad., 19(649), 1983
mouse LD50 oral 1600 mg/kg BEHAVIORAL: ATAXIA; LUNGS, THORAX, OR RESPIRATION: DYSPNEA Medicamentos de Actualidad., 19(649), 1983

[1]. Protective effects of bendazac lysine on early experimental diabetic nephropathy in rats. Acta Pharmacol Sin. 2005 Jun;26(6):721-8.

[2]. PROTECTIVE EFFECTS OF BENDAZAC LYSINE ON DIABETIC PERIPHERAL NEUROPATHY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS. Clin Exp Pharmacol Physiol. 2006 Dec;33(12):1231-8.

Bendazac is a monocarboxylic acid that is glycolic acid in which the hydrogen attached to the 2-hydroxy group is replaced by a 1-benzyl-1H-indazol-3-yl group. Although it has anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties and has been used for the treatment of various inflammatory skin disorders, its principal effect is to inhibit the denaturation of proteins. Its lysine salt is used in the management of cataracts. It has a role as a radical scavenger and a non-steroidal anti-inflammatory drug. It is a member of indazoles and a monocarboxylic acid.

---

Bendazac is an oxyacetic acid. Despite possessing anti-inflammatory, anti-necrotic, choleretic, and anti-lipidemic characteristics, most research has revolved around studying and demonstrating the agent's principal action in inhibiting the denaturation of proteins - an effect that has primarily proven useful in managing and delaying the progression of ocular cataracts [A39863. A39863]. Bendazac, however, has since been withdrawn or discontinued in various international regions due to its capability or risk for eliciting hepatotoxicity in patients although a small handful of regions may continue to have the medication available for purchase and use either as a topical anti-inflammatory/analgesic cream or eye drop formulation.

---

Drug Indication
Prior to the withdrawal of bendazac from various international regions of use due to concerns for hepatotoxicity the chemical had demonstrated potential usefulness predominantly as the prescription medication bendazac lysine for the indication of managing the level of vision in patients with mild to moderate cataracts to facilitate delaying the need for surgical intervention. Elsewhere bendazac may still be available in a limited capacity as a non-prescription topical cream product for treating conditions like local pain, inflammation, dermatitis, eczema, pruritis, hives, insect bites, burns, erythema, and others - although such products may also be facing general discontinuation.

---

Pharmacodynamics
Bendazac principally demonstrates an antidenaturant action on proteins. This effect has been shown to inhibit the denaturation of various proteins like ocular lens proteins by heat, ultraviolet radiation, free radicals, and other chemicals. The medication may be administered to patients via a number of different formulations, including orally as the lysine salt, as eye drops, or even topical applications for the skin. Some preliminary studies have suggested that an apparent improvement of the blood-retinal barrier had been observed in diabetic patients using bendazac lysine 500 mg three times a day for three to six months. Moreover, the use of topical bendazac has also been shown to demonstrate anti-inflammatory effects in animal models and clinical studies to effectively treat varied dermatoses, especially those involving a necrotic component. Additionally, bendazac has also demonstrated choleretic and antilipidaemic activities that have resulted in substantial reductions in beta/alpha lipoprotein ratio, and total lipid, total cholesterol, and triglyceride levels in patients with dyslipidaemia using oral bendazac lysine 500 mg three times daily. The medication has also elicited the inhibition of phytohaemagglutinin induced lymphocyte transformation in vitro.

---

Mechanism of Action
Bendazac seems to elicit an anticataract action by inhibiting the denaturation of ocular lens proteins, although the precise mechanisms by which this action occurs has not yet been formally elucidated - despite there being many proposed mechanisms. In particular, the denaturation of lens proteins may in part be prevented by inhibiting the binding of certain chemicals like cyanates or sugars and 5-hydroxybendazac - the major metabolite of bendazac - has been shown to be capable of inhibiting the glycosylation of lens proteins by sugars like galactose or glucose-6-phosphate in a dose-dependent manner. Moreover, the apparent ability for administered bendazac to elicit free radical scavenger activities due to interactions with protein molecules suggests that the medication may also be able to prevent the oxidation of lens proteins by free radicals in the development of cataracts. Furthermore, bendazac may also be capable of reducing the sulfhydryl group oxidation of lens proteins by the saliva, serum, or urine from patients with cataracts following single dose administration and reduce biological liquid oxidant activity (BLOA) in doing so. Otherwise, it is believed that bendazac also possesses non-steroidal anti-inflammatory actions, as well as analgesic, antipyretic, and platelet-inhibitory effects These effects may be accounted for in part by the substance's capability to inhibit prostaglandin synthesis by inhibiting cyclooxygenase activity in converting arachidonic acid to cyclic endoperoxides - the precursors of prostaglandins.

C16H14N2O3.C6H14N2O2

428.48152

428.205

C, 61.67; H, 6.59; N, 13.08; O, 18.67

81919-14-4

Bendazac;20187-55-7

13041095

Typically exists as White to off-white solid at room temperature

698.4ºC at 760 mmHg

178-181ºC

376.2ºC

3.475

4

8

10

31

463

1

[C@@H](N)(C(=O)O)CCCCN.C(C1C=CC=CC=1)N1N=C(OCC(=O)O)C2C=CC=CC1=2

OCOCFNMFLNFNIA-ZSCHJXSPSA-N

InChI=1S/C16H14N2O3.C6H14N2O2/c19-15(20)11-21-16-13-8-4-5-9-14(13)18(17-16)10-12-6-2-1-3-7-12;7-4-2-1-3-5(8)6(9)10/h1-9H,10-11H2,(H,19,20);5H,1-4,7-8H2,(H,9,10)/t;5-/m.0/s1

2-(1-benzylindazol-3-yl)oxyacetic acid;(2S)-2,6-diaminohexanoic acid

Bendazac L-lysine; Bendazac lysine; 81919-14-4; Bendalina; Bendaline; Bendazaco lisina; bendazac lysine salt; AF 1934;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

H2O : ~25 mg/mL (~58.35 mM)

Solubility in Formulation 1: 50 mg/mL (116.69 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)