targeted-toxins

Dobryakova YV, Volobueva MN, Manolova AO, Medvedeva TM, Kvichansky AA, Gulyaeva NV, Markevich VA, Stepanichev MY, Bolshakov AP (2019) Cholinergic deficit induced by central administration of 192IgG-Saporin is associated with activation of microglia and cell loss in the dorsal hippocampus of rats. Front Neurosci 13:146. doi: 10.3389/fnins.2019.00146

Objective: To study the histopathology of the hippocampus and the responses of microglia and astrocytes using immunohistochemistry and neuroglial gene expression.

Summary: Cholinergic degeneration in the medial septal area induced by intracerebroventricular administration of 192IgG-saporin results in an increase in the number of microglial cells and neuron degeneration in the dorsal hippocampus.

Usage: 192-IgG-SAP was injected bilaterally into both ventricles (i.c.v.) at a dose of 4 μg/site.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Bahari Z, Meftahi GH (2019) Spinal α2-adrenoceptors and neuropathic pain modulation; therapeutic target. Br J Pharmacol 176(14):2366-2381. doi: 10.1111/bph.14580

Objective: To provide an an overview of the cellular mechanisms through which brainstem adrenergic descending inhibitory processing can alter spinal pain transmission to the higher centres, and how these pathways change in neuropathic pain conditions focusing on the role of spinal α2‐adrenoceptors in the spinal dorsal horn.

Summary: The α2‐adrenoceptor agonist may be useful to treat neuropathic pain.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Devoto P, Flore G, Saba P, Scheggi S, Mulas G, Gambarana C, Spiga S, Gessa GL (2019) Noradrenergic terminals are the primary source of α2-adrenoceptor mediated dopamine release in the medial prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 90:97-103. doi: 10.1016/j.pnpbp.2018.11.015

Objective: To clarify the relative contribution of dopamine (DA) release from noradrenergic and dopaminergic terminals to DA output induced by blockade of α2-adrenoreceptors and the norepinephrine transporter.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Nirogi R, Shinde A, Mohammed AR, Badange RK, Reballi V, Bandyala TR, Saraf SK, Bojja K, Manchineella S, Achanta PK, Kandukuri KK, Subramanian R, Benade V, Palacharla RC, Jayarajan P, Pandey S, Jasti V (2019) Discovery and development of N-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A novel, potent, selective, and orally active histamine H3 receptor inverse agonist with robust wake-promoting activity. J Med Chem 62(3):1203-1217. doi: 10.1021/acs.jmedchem.8b01280

Objective: To discover and develop a therapeutic for human sleep disorders.

Summary: Histamine H3 Receptor Inverse Agonist demonstrated high receptor occupancy and marked wake promoting effects with decreased REM sleep in Orexin-B-SAP lesioned rats. This study supports its potential therapeutic utility in treating human sleep disorders.

Usage: Injections (490 ng/0.8 μl) were made bilaterally to the lateral hypothalamus.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Czechowicz A, Palchaudhuri R, Scheck A, Hu Y, Hoggatt J, Saez B, Pang WW, Mansour MK, Tate TA, Chan YY, Walck E, Wernig G, Shizuru JA, Winau F, Scadden DT, Rossi DJ (2019) Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617. doi: 10.1038/s41467-018-08201-x

Objective: To investigate a safe and effective method for hematopoietic stem cell transplantation.

Summary: CD117-ADC selectively targets hematopoietic stem cells yet does not cause clinically significant side-effects.

Usage: The CD117-ADC was prepared by combining biotinylated anti-CD117 (clone 2B8) with Streptavidin–ZAP. A dose of 1.5 mg/kg of CD117-ADC (~12 µg Streptavidin-ZAP) optimally resulted in depletion of >99% of immunophenotypic and functional HSCs.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)

Andrade DC, Toledo C, Díaz HS, Lucero C, Arce-Álvarez A, Oliveira LM, Takakura AC, Moreira TS, Schultz HD, Marcus NJ, Alcayaga J, Del Rio R (2019) Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure. Clin Sci (Lond) 133(3):393-405. doi: 10.1042/CS20180589

Objective: To determine the role played by RVLM-C1 neurons in cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction in volume overload-induced heart failure.

Summary: RVLM-C1 neurons were selectively ablated using Anti-DBH-SAP and measures of cardiacautonomictone, function, and arrhythmia incidence were evaluated. Cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction were present in HF rats and improved after Anti-DBH-SAP treatment.

Usage: 7.5ng/100nl of sterile saline solution was injected bilaterally into the RVLM.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Kucinski A, Kim Y, Sarter M (2019) Basal forebrain chemogenetic inhibition disrupts the superior complex movement control of goal-tracking rats. Behav Neurosci 133:121-134. doi: 10.1037/bne0000290

Usage: Basal forebrain cholinergic neurons situated in the nucleus basalis and substantia innominata were targeted with 192-IgG-SAP in aCSF infused bilaterally (200 ng/μL; 0.8 μL/hemisphere).

Related Products: 192-IgG-SAP (Cat. #IT-01)

Pinto LG, Souza GR, Kusuda R, Lopes AH, Sant’Anna MB, Cunha FQ, Ferreira SH, Cunha TM (2019) Non-peptidergic nociceptive neurons are essential for mechanical inflammatory hypersensitivity in mice. Mol Neurobiol 56(8):5715-5728. doi: 10.1007/s12035-019-1494-5

Objective: To determine the role of non-peptidergic nociceptors in mediating mechanical inflammatory hypersensitivity in mice.

Summary: rIB4-SAP oblates non-peptidergic neurons as displayed by the decrease of purinoceptor 3. The depletion of these neurons inhibited the mechanical inflammatory sensitivity induced by GDMF and carrageenan, but not by other expected factors such as nerve growth factor implying the role of this subset of neurons to be one of mediation as opposed to direct nociception.

Usage: IB4-SAP (0.16–3.2 μg/5 μl, i.t.), unconjugated Saporin (as control, 1.8 μg/5 μl, i.t.), or saline (vehicle, 5 μl/i.t.) were injected into the subarachnoid space on the midline between the L5 and L6 vertebrae.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Abadir E, Bryant C, Larsen S, Clark GJ (2019) Targeting the niche: Depleting haemopoietic stem cells with targeted therapy. Bone Marrow Transplant 54:961–968. doi: 10.1038/s41409-019-0445-0

Summary: Anti-mouse CD45 ADC (clone 104-Saporin) Depletes mature lymphoid cells and HSPC, conditioning allows for high level sustained multilineage engraftment of congenic mice. Anti-mouse ADC (CD117-saporin) Combined with T cell depleting agents allowed for significant and durable engraftment in an immunocompetent mouse allo-HSCT model.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)

Xu H, Chen L, Zhang X, Jiang X, Tian W, Yu W, Wang X, Tian J, Su D (2019) Central cholinergic neuronal degeneration promotes the development of postoperative cognitive dysfunction. Lab Invest 99(7):1078-1088. doi: 10.1038/s41374-018-0174-9

Usage: 1 microliter of mu-p75-SAP at a concentration of 0.8 μg/μl was injected into the lateral ventricles.

Related Products: mu p75-SAP (Cat. #IT-16)