NPASS Compound

Natural Product: NPC476153

Natural Product ID	NPC476153
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(S)-7-Hydroxy-5-Methoxy-6-Methyl-4-Oxo-2-Phenyl-Chroman-8-Carbaldehyde
IUPAC Name	(2S)-7-hydroxy-5-methoxy-6-methyl-4-oxo-2-phenyl-2,3-dihydrochromene-8-carbaldehyde
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL54105
PubChem CID	503268
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002590] 5-O-methylated flavonoids

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 39 41 0 0 0 0 0 0 0 0999 V2000 -4.7235 0.6532 0.4120 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2405 0.6914 0.3629 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5439 1.8821 0.4116 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1663 1.9364 0.3671 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4687 0.7333 0.2692 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1806 -0.4594 0.2210 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5585 -0.5076 0.2658 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2803 -1.6903 0.2185 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6430 -2.4233 1.3672 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4736 -1.7312 0.1190 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0617 -2.7894 -0.1486 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0141 -1.6551 0.3627 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5073 -0.4667 -0.3889 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9180 0.6947 0.2188 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9491 -0.3328 -0.4967 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5087 0.8364 -0.9533 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8999 0.9770 -1.0607 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7049 -0.0611 -0.7071 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1786 -1.2291 -0.2524 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7872 -1.3568 -0.1497 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4177 3.1869 0.4176 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0653 3.6477 1.5112 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2229 3.0803 0.5084 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1654 -0.0061 -0.3456 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0232 0.3189 1.4420 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1113 1.7024 0.3078 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8295 -3.4662 1.0370 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6165 -2.0328 1.7326 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8587 -2.4000 2.1491 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4619 -2.6128 0.0322 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2310 -1.5107 1.4424 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1039 -0.4762 -1.4460 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8918 1.6786 -1.2415 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3469 1.8893 -1.4173 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7981 0.0406 -0.7884 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8373 -2.0528 0.0274 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4575 -2.3087 0.2174 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1547 3.7369 -0.4903 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7904 3.8827 0.9768 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 6 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 4 21 1 0 21 22 2 0 3 23 1 0 7 2 1 0 14 5 1 0 20 15 1 0 1 24 1 0 1 25 1 0 1 26 1 0 9 27 1 0 9 28 1 0 9 29 1 0 12 30 1 0 12 31 1 0 13 32 1 0 16 33 1 0 17 34 1 0 18 35 1 0 19 36 1 0 20 37 1 0 21 38 1 0 23 39 1 0 M END

Standard InCHIKey	LSODPLCBFFZIHL-AWEZNQCLSA-N
Standard InCHI	InChI=1S/C18H16O5/c1-10-16(21)12(9-19)18-15(17(10)22-2)13(20)8-14(23-18)11-6-4-3-5-7-11/h3-7,9,14,21H,8H2,1-2H3/t14-/m0/s1
SMILES	CC1=C(C(=C2C(=C1OC)C(=O)CC(O2)C3=CC=CC=C3)C=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	312.1	Volume:	317.074 ? Van der Waals volume.
Dense:	0.984	LogP:	3.31 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.086 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.17 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	19.0
TPSA:	72.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.881	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.125	Fsp³:	0.222
MCE-18:	57.273 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.632	Fluc inhibitor:	0.156 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.412 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.652 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.253	Promiscuous compounds:	0.007

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.035	MDCK Permeability:	-4.793
Pgp-inhibitor:	0.981	Pgp-substrate:	0.005
PAMPA:	0.331 ? 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):	0.042
20% Bioavailability (F20%):	0.037	30% Bioavailability (F30%):	0.289
50% Bioavailability (F50%):	0.54

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.515	MRP1:	0.875
Plasma Protein Binding (PPB):	98.468%	Volume Distribution (VD):	-0.277
Fu:	1.031% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.781
OATP1B3 inhibitor:	0.921	BCRP inhibitor:	0.327
BSEP inhibitor:	0.979

ADMET: Metabolism

CYP1A2-inhibitor:	0.815	CYP1A2-substrate:	0.998
CYP2C19-inhibitor:	0.434	CYP2C19-substrate:	0.928
CYP2C9-inhibitor:	0.66	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.057	CYP2D6-substrate:	0.771
CYP3A4-inhibitor:	0.205	CYP3A4-substrate:	0.347
CYP2B6-substrate:	0.003	CYP2C8-inhibitor:	0.287
HLM stability:	0.307 ? 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):

2.239

Half-life (T1/2):

1.353

ADMET: Toxicity

hERG Blockers:	0.121	hERG Blockers (10um):	0.532
Human Hepatotoxicity (H-HT):	0.686	Drug-induced Liver Injury (DILI):	0.411
AMES Toxicity:	0.522	Rat Oral Acute Toxicity:	0.514
Maximum Recommended Daily Dose:	0.504	Skin Sensitization:	0.818
Carcinogencity:	0.665	Eye Corrosion:	0.073
Eye Irritation:	0.969	Respiratory Toxicity:	0.536
Drug-induced Neurotoxicity:	0.664	Ototoxicity:	0.27
Hematotoxicity:	0.34	Drug-induced Nephrotoxicity:	0.52
Genotoxicity:	0.584	RPMI-8226 Immunitoxicity:	0.088
A549 Cytotoxicity:	0.278	Hek293 Cytotoxicity:	0.448
BCF:	1.403 ? 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:	4.26 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.673 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.164 ? 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
NPO33071	desmos spp.	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12729671]

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	1
EC50	1

Activity Type	# Activity
Cell line	2

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT759	Cell line	H9	Homo sapiens	IC50	=	108.0	ug.mL-1	PMID[12542345]
NPT759	Cell line	H9	Homo sapiens	EC50	=	11.0	ug.mL-1	PMID[12542345]

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 NPC476153 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	24264
0.1-0.2	22005
0.2-0.3	3186
0.3-0.4	279
0.4-0.5	86
0.5-0.6	24
0.6-0.7	9
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	Natural Product ID
0.7115	Intermediate Similarity	NPC2416
0.7059	Intermediate Similarity	NPC215885
0.6863	Remote Similarity	NPC177354
0.6731	Remote Similarity	NPC110776
0.6731	Remote Similarity	NPC110038
0.6346	Remote Similarity	NPC248372
0.6275	Remote Similarity	NPC265871
0.6275	Remote Similarity	NPC205093
0.6182	Remote Similarity	NPC471621
0.6182	Remote Similarity	NPC271590
0.6154	Remote Similarity	NPC22467
0.5849	Remote Similarity	NPC213322
0.5818	Remote Similarity	NPC194432
0.5741	Remote Similarity	NPC482121
0.5741	Remote Similarity	NPC270964
0.56	Remote Similarity	NPC228184
0.5536	Remote Similarity	NPC296917
0.5536	Remote Similarity	NPC170907
0.5439	Remote Similarity	NPC485881
0.5397	Remote Similarity	NPC316816
0.5323	Remote Similarity	NPC3642
0.5273	Remote Similarity	NPC225153
0.5273	Remote Similarity	NPC188243
0.5273	Remote Similarity	NPC479876
0.5273	Remote Similarity	NPC110228
0.5263	Remote Similarity	NPC482119
0.5263	Remote Similarity	NPC482120
0.5179	Remote Similarity	NPC482487
0.5161	Remote Similarity	NPC109183
0.5088	Remote Similarity	NPC150648
0.5088	Remote Similarity	NPC312391
0.5088	Remote Similarity	NPC37392
0.5088	Remote Similarity	NPC167624
0.5088	Remote Similarity	NPC166482
0.5079	Remote Similarity	NPC175504

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476153 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3624
0.1-0.2	5330
0.2-0.3	186
0.3-0.4	7
0.4-0.5	3
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