NPASS Compound

Natural Product: NPC154256

Natural Product ID	NPC154256
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S)-2-(Hydroxymethyl)-2-Methylchromen-6-Ol
IUPAC Name	(2S)-2-(hydroxymethyl)-2-methylchromen-6-ol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL232615
PubChem CID	44431346
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 26 27 0 0 0 0 0 0 0 0999 V2000 -3.6774 0.6632 0.5453 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6310 0.7064 -0.3416 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6224 -0.3830 0.0345 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3221 -1.7252 -0.0895 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2035 -0.1749 1.4287 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0344 0.0695 1.7997 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0572 0.1380 0.7557 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7589 -0.0437 -0.5768 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5771 -0.2994 -0.8954 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7095 0.0166 -1.5816 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0145 0.2705 -1.2288 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3363 0.4557 0.0984 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3792 0.3927 1.0874 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6416 0.7157 0.5124 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0418 1.5871 0.6228 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9092 0.5711 -1.3961 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0722 1.6727 -0.2133 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3908 -1.5996 0.1610 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8828 -2.4287 0.6237 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2119 -2.1271 -1.1109 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9553 -0.2257 2.1918 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2989 0.2164 2.8381 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4329 -0.1319 -2.6145 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8164 0.3328 -1.9614 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5989 0.5335 2.1391 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4187 0.7974 -0.1207 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 3 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 8 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 9 3 1 0 13 7 1 0 1 15 1 0 2 16 1 0 2 17 1 0 4 18 1 0 4 19 1 0 4 20 1 0 5 21 1 0 6 22 1 0 10 23 1 0 11 24 1 0 13 25 1 0 14 26 1 0 M END

Standard InCHIKey	LTKJWSBGTNWRNP-NSHDSACASA-N
Standard InCHI	InChI=1S/C11H12O3/c1-11(7-12)5-4-8-6-9(13)2-3-10(8)14-11/h2-6,12-13H,7H2,1H3/t11-/m0/s1
SMILES	OC[C@]1(C)C=Cc2c(O1)ccc(c2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	192.08	Volume:	197.524 ? Van der Waals volume.
Dense:	0.972	LogP:	2.037 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.037 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.088 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	11.0
TPSA:	49.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.709	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.281	Fsp³:	0.273
MCE-18:	37.714 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.099	Fluc inhibitor:	0.05 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.116 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.195 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.873	Promiscuous compounds:	0.456

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.011	MDCK Permeability:	-4.764
Pgp-inhibitor:	0.005	Pgp-substrate:	0.473
PAMPA:	0.937 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.03
20% Bioavailability (F20%):	0.72	30% Bioavailability (F30%):	0.751
50% Bioavailability (F50%):	0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.394	MRP1:	0.595
Plasma Protein Binding (PPB):	74.663%	Volume Distribution (VD):	0.125
Fu:	29.509% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.872
OATP1B3 inhibitor:	0.764	BCRP inhibitor:	0.143
BSEP inhibitor:	0.164

ADMET: Metabolism

CYP1A2-inhibitor:	0.098	CYP1A2-substrate:	0.306
CYP2C19-inhibitor:	0.258	CYP2C19-substrate:	0.04
CYP2C9-inhibitor:	0.905	CYP2C9-substrate:	0.197
CYP2D6-inhibitor:	0.872	CYP2D6-substrate:	0.35
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	0.645
CYP2B6-substrate:	0.013	CYP2C8-inhibitor:	0.918
HLM stability:	0.694 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

10.166

Half-life (T1/2):

1.495

ADMET: Toxicity

hERG Blockers:	0.143	hERG Blockers (10um):	0.461
Human Hepatotoxicity (H-HT):	0.778	Drug-induced Liver Injury (DILI):	0.271
AMES Toxicity:	0.489	Rat Oral Acute Toxicity:	0.5
Maximum Recommended Daily Dose:	0.33	Skin Sensitization:	0.938
Carcinogencity:	0.746	Eye Corrosion:	0.104
Eye Irritation:	0.991	Respiratory Toxicity:	0.417
Drug-induced Neurotoxicity:	0.371	Ototoxicity:	0.288
Hematotoxicity:	0.135	Drug-induced Nephrotoxicity:	0.331
Genotoxicity:	0.36	RPMI-8226 Immunitoxicity:	0.084
A549 Cytotoxicity:	0.088	Hek293 Cytotoxicity:	0.23
BCF:	0.605 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	2.472 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.641 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.111 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO21659	Daedalea quercina	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11014261]
NPO20918	Pseudotsuga menziesii	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34216094]
NPO20795	Melicope melanophloia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21659	Daedalea quercina	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22868	Pulsatilla dahurica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13371	Paepalanthus ramosus	Species	Eriocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20918	Pseudotsuga menziesii	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21268	Heliotropium ramosissimum	Species	Heliotropiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21268	Heliotropium ramosissimum	Species	Heliotropiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22868	Pulsatilla dahurica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18205	Brevibacterium iodinum	Species	Brevibacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO20795	Melicope melanophloia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20918	Pseudotsuga menziesii	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20036	Mallotus pallidus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13371	Paepalanthus ramosus	Species	Eriocaulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22868	Pulsatilla dahurica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21659	Daedalea quercina	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25850	Urochloa ruziziensis	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21268	Heliotropium ramosissimum	Species	Heliotropiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	5

Activity Type	# Activity
Individual protein	4
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	IC50	=	4700.0	nM	PMID[17346963]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	IC50	=	630.0	nM	PMID[17346963]
NPT967	Individual protein	Xanthine dehydrogenase	Homo sapiens	IC50	=	21000.0	nM	PMID[17346963]
NPT4734	Individual protein	Dehydrogenase/reductase SDR family member 9	Homo sapiens	IC50	=	114000.0	nM	PMID[17346963]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	=	68000.0	nM	PMID[17346963]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC154256 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	17866
0.1-0.2	26903
0.2-0.3	4946
0.3-0.4	131
0.4-0.5	9
0.5-0.6	1
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC290470
0.6	Remote Similarity	NPC474920
0.566	Remote Similarity	NPC476165

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC154256 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4270
0.1-0.2	4703
0.2-0.3	174
0.3-0.4	3
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data