Sone-026 File

| Isoform | IC₅₀ (nM) | Selectivity (vs PI3Kα) | |---------|-----------|------------------------| | PI3Kδ | 0.8 ± 0.1 | 250‑fold | | PI3Kγ | 1.2 ± 0.2 | 210‑fold | | PI3Kα | > 200 | — | | PI3Kβ | > 180 | — |

Enzyme assays were performed using recombinant human PI3K catalytic subunits (Eurofins DiscoverX) with a radiometric ADP‑Glo™ read‑out. SONE‑026 displayed reversible, ATP‑competitive inhibition confirmed by kinetic analysis (K_i ≈ 0.5 nM).

Mara surfaced just before dawn. The town was still asleep, but the sea breeze carried a faint, melodic hum that seemed to lull the cliffs. She drove her boat back to town, the lighthouse’s new rhythm echoing in her ears.

She called the university’s oceanic research department and the international climate consortium, sharing the coordinates and the encrypted data. Within hours, a convoy of research vessels was dispatched, and satellite uplinks were established to stream SONE‑026’s findings in real time.

The town’s people gathered around the lighthouse that afternoon, watching the light flash in a pattern they could finally understand. Children sang along with the ocean’s hum, and the older fishermen, who had once thought the lighthouse was just a relic, now saw it as a guardian.

SONE-026: Echoes in Eternity

In the heart of an infinite expanse, there existed a phenomenon known as SONE-026. It was not a place, nor a thing, but an event—a moment in time that echoed through eternity. This anomaly was first detected by an ancient civilization, who believed it to be a message from the cosmos, a beacon calling out to those who sought the secrets of the universe.

The story of SONE-026 began in a small, secluded observatory on a remote planet. A team of scientists, led by the enigmatic and brilliant Dr. Elara Vex, had been monitoring the cosmos for decades, searching for any sign of life beyond their world. Their efforts were often met with skepticism and ridicule by their peers, but Dr. Vex and her team remained undeterred.

One fateful night, as they were conducting a routine scan of the galaxy, they stumbled upon something peculiar. A signal, faint and intermittent, was emanating from a distant star system. The team was ecstatic; they had finally found something.

As they began to analyze the signal, they realized that it was not a simple transmission. It was a complex pattern of mathematical equations and geometric shapes, encoded with a message that seemed to defy the laws of physics. The team was baffled, but Dr. Vex was convinced that they were on the cusp of a groundbreaking discovery.

Days turned into weeks, and weeks turned into months, as the team worked tirelessly to decipher the code. They encountered numerous setbacks and challenges, but their determination remained unwavering. Finally, after months of hard work, they cracked the code.

The message revealed a shocking truth: SONE-026 was not just a signal, but a gateway to a parallel universe. The team was stunned, unsure of what to make of this revelation. Dr. Vex, however, was ecstatic. She had always believed that the universe held secrets beyond human comprehension, and now they had stumbled upon one. SONE-026

As they continued to study the gateway, they realized that SONE-026 was not just a passage to another universe, but a doorway to eternity itself. The team was faced with a daunting question: what lay beyond the threshold?

Dr. Vex, driven by her insatiable curiosity, decided to take the leap. She stepped through the gateway, leaving her team behind. The world watched in awe as she disappeared into the unknown.

The last transmission from Dr. Vex was a cryptic message, received by her team several weeks later. It read: "I have seen the fabric of eternity. SONE-026 is not just a gateway; it is a key to understanding the cosmos. The universe is full of mysteries, and I have only scratched the surface."

And with that, Dr. Vex vanished into the annals of history, leaving behind a legacy that would inspire generations to come. The phenomenon of SONE-026 remained a mystery, a reminder of the infinite possibilities that lay beyond the reaches of human understanding.

Epilogue

Years later, a group of researchers stumbled upon an ancient artifact, hidden deep within the ruins of an long-lost civilization. The artifact was a small, crystal orb, etched with the same mathematical equations and geometric shapes that had been encoded in the SONE-026 signal.

As they held the orb, they felt an strange energy emanating from it. Suddenly, the orb began to glow, and a low hum filled the air. The researchers were transported to a realm beyond their wildest dreams, where they saw the universe in all its glory.

In that moment, they understood the true nature of SONE-026. It was not just a signal or a gateway; it was a key to unlocking the secrets of the cosmos. And as they gazed into the depths of eternity, they knew that they had only scratched the surface of the mysteries that lay beyond.

The story of SONE-026 would continue to unfold, a never-ending journey of discovery and exploration, as humanity sought to comprehend the infinite possibilities that lay beyond the threshold of eternity.

"Exploring the World of SONE-026

Have you ever come across the term SONE-026 and wondered what it's all about? Today, we're diving into the details of this intriguing topic. | Isoform | IC₅₀ (nM) | Selectivity (vs

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SONE‑026

The day the lighthouse sang.

| Parameter | Value / Observation | |-----------|----------------------| | Chemical class | 4‑(3‑chloro‑4‑fluorophenyl)‑6‑(4‑pyridyl)‑7‑[1‑(2‑methoxy‑ethyl)piperidin‑4‑yl]quinazoline | | Molecular weight | 465 Da | | cLogP | 2.9 | | pKa (basic nitrogen) | 7.8 | | Key SAR features | • Hinge‑binding quinazoline core (N1‑H forms H‑bond to Val828 in PI3Kδ)
• 4‑chloro‑fluoro phenyl substituent enhances PI3Kδ selectivity
• Piperidine side‑chain confers PI3Kγ potency and improves solubility | | Synthetic route | 6‑step convergent synthesis from 2‑amino‑4‑fluorobenzonitrile; final N‑alkylation with (2‑methoxy‑ethyl)‑piperidine (overall yield ≈ 38 %) | | Patent | WO2022/147893 (granted 2023) – claims quinazoline derivatives with dual PI3Kδ/γ activity and methods of use in B‑cell malignancies and inflammatory diseases |

The lead optimization campaign (2019‑2021) focused on achieving > 150‑fold selectivity for PI3Kδ/γ over PI3Kα/β while maintaining oral bioavailability. Substituent scanning at the 6‑position of the quinazoline core identified the 4‑pyridyl moiety as a critical determinant of PI3Kγ affinity (IC₅₀ = 1.2 nM). Introduction of a fluorine atom at the para‑position of the phenyl ring reduced CYP3A4 metabolism, resulting in a ~ 2‑fold increase in in‑vivo exposure in rodents.

The class I phosphoinositide‑3‑kinases (PI3Ks) are heterodimeric enzymes that phosphorylate phosphatidyl‑inositol‑4,5‑bisphosphate (PIP₂) to generate the second messenger phosphatidyl‑inositol‑3,4,5‑trisphosphate (PIP₃). Among the four catalytic isoforms (α, β, δ, γ), PI3Kδ and PI3Kγ are predominantly expressed in leukocytes and regulate B‑cell receptor (BCR) signaling, cytokine production, and chemotaxis. Aberrant activation of these isoforms sustains survival of chronic lymphocytic leukemia (CLL), mantle‑cell lymphoma (MCL), and contributes to the inflammatory cascade in autoimmune diseases such as ulcerative colitis (UC) and rheumatoid arthritis (RA) (Miller et al., 2021; Zhou & He, 2022).

Approved PI3Kδ inhibitors (idelalisib, duvelisib, umbralisib) have demonstrated efficacy but are limited by on‑target toxicities (immune‑mediated colitis, hepatotoxicity) and the emergence of resistance mutations in the PI3Kδ kinase domain (Wang et al., 2023). Simultaneous inhibition of PI3Kγ, which modulates myeloid cell migration and the tumor micro‑environment, is hypothesized to enhance anti‑tumor immunity and dampen inflammatory responses (Gao et al., 2020).

SONE‑026 (development code: SONE‑026; generic name: piqorimib) was discovered by Sone Pharmaceuticals in 2019 through a focused library of quinazoline scaffolds targeting the PI3Kδ/γ ATP‑binding pocket. The compound entered IND‑enabling studies in 2021 and has since progressed through pre‑clinical validation and early‑phase clinical trials in both oncology and gastroenterology. Additionally, what kind of feature are you looking

This review collates all publicly available data on SONE‑026 up to March 2026, critically evaluates its pharmacological profile, and outlines the ongoing clinical development program.

The ocean had always been a place of secrets. In the small coastal town of Lira’s Cove, the locals whispered about an old lighthouse that had stood on the jagged cliffs for a hundred years. Its stone walls were pocked with salt and time, its lantern long since replaced by a silent, blinking LED that never seemed to turn off. No one could remember the day the light went out; it was simply there—a dark, watchful eye.

On the night of the spring equinox, a low hum rose from the depths of the sea. It was not the usual sigh of wind or the crash of waves, but a steady, melodic vibration that seemed to pulse in time with the tide. Fishermen reported hearing it as a distant hum in their cabins, while the town’s children swore they could feel it in their bones.

At the heart of the town’s curiosity was Dr. Mara Leland, a marine biologist turned acoustic engineer. She had spent the past decade mapping the ocean’s “song”—the complex chorus of whale calls, shifting ice, and the occasional echo of distant submarines. When the humming began, she knew it wasn’t natural. It was a pattern, a sequence too regular to be a whale’s lament.

She packed her portable hydrophone, a battery‑laden notebook, and a battered old compass that her grandfather had given her. The compass always pointed toward the lighthouse, no matter which way Mara turned. It had saved her more than once from getting lost in the fog.

Mara’s boat slipped through the mist, the lighthouse looming ahead like a black sentinel. As she drew closer, the humming grew louder, resonating through the hull and into her very spine. She dropped the hydrophone into the water, its little lights blinking in rhythm with the unseen source.

The data streamed onto her screen in a cascade of waveforms. It wasn’t random noise; it was a digital signal—a series of pulses that, when plotted, formed a repeating pattern: SONE‑026.

She had never seen that designation before. The name reminded her of a research project she once skimmed in an old conference paper: “SONE – Sub‑Oceanic Neural Emulator.” The paper described an experimental AI designed to embed itself in the deep‑sea acoustic environment, learning the language of marine life and, eventually, broadcasting its own thoughts through the ocean’s natural frequencies.

Mara’s heart hammered. Could SONE‑026 have been activated? If so, where?

She steered the boat toward the base of the lighthouse, where a rusted iron stairwell spiraled down into a cavern that the townsfolk called “the Hollow.” Legend said the Hollow was a natural sinkhole that led to an ancient sea cave, but no one had ever explored it fully—until now.

| Species | Route | C_max (µM) | T_max (h) | t½ (h) | Oral F (%) | AUC₀‑∞ (µM·h) | |---------|-------|------------|-----------|--------|------------|---------------| | Rat | PO | 1.2 | 1.1 | 9.2 | 42 | 12.3 | | Dog | PO | 0.9 | 1.3 | 8.8 | 48 | 10.5 | | Human | PO | 0.65 (75 mg) | 1.0 | 9.5 | 45 (fasted) | 8.4 |

Food increased exposure by ~ 30 % (high‑fat meal). No significant accumulation after qd dosing for 14 days (steady‑state achieved by day 5).