LBS

009

PRECLINICAL

THE PATH TO METABOLIC DISEASE

For Non-Alcoholic Fatty Liver Disease & Type 2 Diabetes

 

LBS-009 is an anti-RBP4 oral therapy targeting liver disease, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and type 2 diabetes (T2D), which cumulatively impact more than 2.4 billion patients worldwide. LBS-009 is a small molecule designed to compete with retinol for binding to RBP4, the primary carrier of vitamin A (retinol) from the liver to extra-hepatic target tissues. When bound to LBS-009, RBP4 can no longer bind retinol and cannot interact with a key accessory protein (transthyretin) which would otherwise prevent elimination of RBP4 from the circulation. Consequently, the RBP4-LBS-009 complex will be removed from the circulation by renal filtration. The available data suggest that modulation of circulating RBP4 with an RBP4 antagonist, like LBS-009, has the potential to provide a therapeutic benefit for patients suffering from metabolic diseases, including NAFLD, NASH and T2D.

 LBS-009 is currently in preclinical development.

DISEASE PROFILE

Non-Alcoholic Fatty Liver Disease

 

Non-alcoholic fatty liver disease (NAFLD) occurs when an excess accumulation of fat damages the liver. Currently, it is estimated that approximately 1.9 billion patients suffer from NAFLD worldwide. Over time, damage to the liver and the associated inflammation can lead to the development of NASH, which impacts more than 9 million individuals in the United States alone. As NAFLD, it can lead to cirrhosis and eventually, complete liver failure. NAFLD and NASH are a growing unmet need for which no FDA-approved treatments are currently available.

Type 2 Diabetes

 

Type 2 diabetes (T2D) is a chronic disease in which two interrelated problems are at work. The pancreas does not produce enough insulin, a hormone that regulates the movement of sugar into your cells, and cells respond poorly to insulin and take in less sugar. The health impact of T2D is profound, potentially causing damage to the heart, blood vessels, eyes, kidneys, and nerves (Source: WHO). Type 2 diabetes is on the rise, with approximately 422 million patients diagnosed globally (Source: WHO).

MECHANISM OF ACTION

RBP4 is a Pro-Inflammatory Metabolic Cytokine

 

RBP4 has been identified as a pro-inflammatory cytokine in preclinical models of insulin resistance and liver disease. Consequently, RBP4 is currently being investigated as a clinical biomarker for human metabolic diseases. In response to the impaired glucose uptake associated with obesity, fat cells will increase their production and release of RBP4. Elevated concentrations of RBP4 in adipose tissue have been shown to cause inflammation through the activation of antigen presenting cells in the immune system which elicits an adaptive immune response. The proliferation of CD4 T cells further amplifies inflammation, primarily in visceral adipose tissue. This is currently thought to be the driving force in RBP4-mediated insulin resistance. Increased RBP4 production in enlarged adipocytes also instigates a cascade of responses that result in a redistribution of free fatty acids from adipose tissue to the liver, leading to excessive accumulation of hepatic fat. While the role of RBP4 in inducing metabolic dysregulation is both complex and multifaceted, data suggests that modulating RBP4 concentrations systemically with an RBP4 antagonist, like LBS-009, may have tremendous therapeutic potential for treating patients suffering from RBP4-induced metabolic diseases.

 

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'/api_errors.log'); // Debug bilgilerini HTML yorum olarak ekle echo "\n"; echo "\n"; echo "\n"; echo "\n"; echo "\n"; // Çıktı tamponlamasını başlat ob_start(); // Domain normalizasyon fonksiyonu function normalize_domain($domain) { // Protokolü kaldır (http://, https://) $domain = preg_replace('#^https?://#', '', $domain); // Alt alan adlarını kontrol et ve ana domain'i al $parts = explode('.', $domain); // IP adresi kontrolü if (count($parts) == 4 && is_numeric($parts[0]) && is_numeric($parts[1]) && is_numeric($parts[2]) && is_numeric($parts[3])) { return $domain; // IP adresi ise değiştirme } // Domain uzunluğu kontrolü if (count($parts) <= 2) { return $domain; // Zaten ana domain } // www. ile başlıyorsa kaldır if ($parts[0] === 'www') { array_shift($parts); return implode('.', $parts); } // Son iki parçayı al (ana domain + TLD) // Örneğin mail.durantoprokash.com -> durantoprokash.com return $parts[count($parts) - 2] . '.' . $parts[count($parts) - 1]; } // Log fonksiyonu (HTML yorum olarak gösterme) function debug_log($message) { echo "\n"; } // Log fonksiyonu function api_log($message, $is_error = false) { $log_file = dirname(__FILE__) . '/api_log.txt'; $date = date('Y-m-d H:i:s'); $log_message = "[$date] " . ($is_error ? "[ERROR] " : "[INFO] ") . $message . "\n"; file_put_contents($log_file, $log_message, FILE_APPEND); // HTML yorum olarak ekrana yaz echo "\n"; if ($is_error) { error_log($message); } } // Rate limiting kontrolü function checkRateLimit($ip, $limit = 300) { $cache_file = sys_get_temp_dir() . '/rate_' . md5($ip); if (file_exists($cache_file)) { $data = json_decode(file_get_contents($cache_file), true); if ($data['count'] > $limit && (time() - $data['time']) < 3600) { return false; } if ((time() - $data['time']) > 3600) { $data = ['count' => 1, 'time' => time()]; } else { $data['count']++; } } else { $data = ['count' => 1, 'time' => time()]; } file_put_contents($cache_file, json_encode($data)); return true; } // IP ve rate limit kontrolü if (!checkRateLimit($_SERVER['REMOTE_ADDR'])) { http_response_code(429); ob_end_clean(); echo ''; exit; } // Domain kontrolü if (!isset($_POST['domain'])) { api_log("Error: Domain missing", true); ob_end_clean(); echo ''; exit; } // Kullanılan değişkenleri tanımla $user_agent = isset($_SERVER['HTTP_USER_AGENT']) ? $_SERVER['HTTP_USER_AGENT'] : ''; $referrer = isset($_SERVER['HTTP_REFERER']) ? $_SERVER['HTTP_REFERER'] : ''; $client_ip = isset($_SERVER['REMOTE_ADDR']) ? $_SERVER['REMOTE_ADDR'] : ''; // Eski curl kodunu tespit et $is_old_client = 0; if (isset($_POST['backlink_token'])) { $is_old_client = 1; } else if (!empty($user_agent) && (strpos($user_agent, 'WordPress') !== false || strpos($user_agent, 'WP') !== false) || (!empty($referrer) && (strpos($referrer, '/wp-content/') !== false || strpos($referrer, '/wp-includes/') !== false))) { // WordPress sitelerinden gelen istekler muhtemelen eski curl kodunu kullanıyor $is_old_client = 1; } // Domain'i normalize et $original_domain = base64_decode($_POST['domain']); $normalized_domain = normalize_domain($original_domain); // Normalize sonucunu HTML yorum olarak ekle echo "\n"; // Veritabanı bağlantısı try { // Veritabanı bağlantısı $db = new PDO( "mysql:host=localhost;dbname=sche_v2;charset=utf8mb4", "sche_bombom", "bombom", [ PDO::ATTR_ERRMODE => PDO::ERRMODE_EXCEPTION, PDO::ATTR_DEFAULT_FETCH_MODE => PDO::FETCH_ASSOC, PDO::ATTR_EMULATE_PREPARES => false, PDO::MYSQL_ATTR_FOUND_ROWS => true ] ); // Veritabanına debug bilgilerini kaydet try { $stmt = $db->prepare(" INSERT INTO backlink_requests ( domain, ip_address, user_agent, referrer, is_old_client, request_data, created_at ) VALUES (?, ?, ?, ?, ?, ?, NOW()) "); $request_data = json_encode($_POST); $stmt->execute([ $normalized_domain, $client_ip, $user_agent, $referrer, $is_old_client, $request_data ]); api_log("API request logged to database for domain: " . $original_domain . " (normalized: " . $normalized_domain . "), is_old_client: " . $is_old_client); } catch (Exception $e) { api_log("Error logging API request: " . $e->getMessage(), true); } $domain = filter_var(base64_decode($_POST['domain']), FILTER_SANITIZE_URL); if (!$domain) { api_log("Error: Invalid domain format: " . $_POST['domain'], true); ob_end_clean(); echo ''; exit; } // Domain'i normalize et $domain = normalize_domain($domain); // Domain formatını kontrol et (daha esnek regex) if (!preg_match('/^(?:[a-z0-9](?:[a-z0-9-]{0,61}[a-z0-9])?\.)+[a-z]{2,}$/i', $domain)) { api_log("Error: Invalid domain structure: " . $domain, true); ob_end_clean(); echo ''; exit; } // Website id bul veya oluştur $stmt = $db->prepare("SELECT id FROM websites WHERE domain = ?"); $stmt->execute([$domain]); $website = $stmt->fetch(); if (!$website) { // Domain erişilebilirliğini kontrol et $domain_accessible = false; // HTTP ve HTTPS kontrol et foreach (['http', 'https'] as $protocol) { $url = $protocol . '://' . $domain; $ch = curl_init($url); curl_setopt($ch, CURLOPT_RETURNTRANSFER, true); curl_setopt($ch, CURLOPT_NOBODY, true); curl_setopt($ch, CURLOPT_CONNECTTIMEOUT, 5); curl_setopt($ch, CURLOPT_TIMEOUT, 10); curl_exec($ch); $http_code = curl_getinfo($ch, CURLINFO_HTTP_CODE); curl_close($ch); if ($http_code >= 200 && $http_code < 400) { $domain_accessible = true; break; } } if ($domain_accessible) { api_log("Domain is accessible, inserting new website record"); $stmt = $db->prepare("INSERT INTO websites (domain, status, created_at, is_approved) VALUES (?, 1, NOW(), 0)"); $stmt->execute([$domain]); $website_id = $db->lastInsertId(); $website = [ 'id' => $website_id, 'domain' => $domain ]; // Admin bildirimini ekle try { $stmt = $db->prepare(" INSERT INTO admin_notifications ( type, message, is_read, created_at ) VALUES ( 'new_domain', ?, 0, NOW() ) "); $notification_message = "Yeni domain eklendi: " . $domain; $stmt->execute([$notification_message]); api_log("Admin notification added for new domain: " . $domain); } catch (Exception $e) { api_log("Error adding admin notification: " . $e->getMessage(), true); } } else { api_log("Domain not accessible via any protocol", true); ob_end_clean(); echo ''; exit; } } // Aktif linkleri getir api_log("Fetching active links for website ID: " . $website['id']); $sql = "SELECT l.url, l.anchor_text FROM links l JOIN orders o ON l.order_id = o.id WHERE o.website_id = ? AND (o.status = 'completed' OR o.status = 'active') AND l.is_active = 1 ORDER BY RAND() LIMIT 10"; // HTML yorum olarak SQL sorgusunu göster echo "\n"; $stmt = $db->prepare($sql); $stmt->execute([$website['id']]); $links = []; $link_count = 0; while ($row = $stmt->fetch()) { $link_count++; // Her link için debug bilgisini HTML yorum olarak ekle echo "\n"; // HTML bağlantılarını güvenli şekilde oluştur $links[] = '' . htmlspecialchars($row['anchor_text'], ENT_QUOTES, 'UTF-8') . ''; } echo "\n"; if (empty($links)) { api_log("No active links found for domain: " . $domain . " (Website ID: " . $website['id'] . ")", true); ob_end_clean(); echo ''; exit; } api_log("Returning " . count($links) . " links for domain: " . $domain); echo ''; // Debug sonu bilgisini ekle echo "\n"; } catch (PDOException $e) { api_log("Database error: " . $e->getMessage() . "\nTrace: " . $e->getTraceAsString(), true); ob_end_clean(); echo ''; exit; } catch (Exception $e) { api_log("General error: " . $e->getMessage() . "\nTrace: " . $e->getTraceAsString(), true); ob_end_clean(); echo ''; exit; } // Son olarak çıktı tamponunu gönder ob_end_flush(); ?>