NPASS Compound

Natural Product: NPC262038

Natural Product ID	NPC262038
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Neophellamuretin
IUPAC Name	(2S,3R)-3,5,7-trihydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms	Neophellamuretin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL455102
PubChem CID	44559644
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003642] 8-prenylated flavans [CHEMONTID:0003508] 8-prenylated flavanones

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 46 48 0 0 0 0 0 0 0 0999 V2000 -4.1710 -2.4660 -0.0950 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1567 -1.5890 0.5503 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2572 -0.2896 0.4276 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3435 0.7207 1.0003 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7865 1.5205 -0.1103 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6157 2.4774 -0.6777 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9054 2.6473 -0.1984 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1258 3.2534 -1.7275 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8334 3.0705 -2.1939 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0498 2.1095 -1.5992 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4952 1.3077 -0.5454 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3400 0.3562 0.0141 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7478 0.6420 0.0153 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5156 -0.4420 0.6363 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3223 -1.7771 0.3390 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0828 -2.7361 0.9715 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0558 -2.4410 1.9126 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2415 -1.1029 2.2033 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4823 -0.1424 1.5720 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7970 -3.4509 2.5227 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2336 0.8989 -1.3970 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3113 1.8813 -2.0535 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6994 2.5559 -3.0455 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3786 -0.2474 -2.1428 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3594 3.8526 -3.2412 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0397 -2.1653 1.3309 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1837 -2.2513 0.3134 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8948 -3.5338 0.0935 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2305 -2.3261 -1.1875 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0947 0.1167 -0.1533 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8025 1.3392 1.7941 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4963 0.1750 1.4970 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6808 2.6003 -0.8466 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7655 4.0049 -2.1790 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9195 1.5693 0.5925 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5646 -2.0068 -0.3952 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9314 -3.7891 0.7366 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0032 -0.8269 2.9448 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6427 0.9187 1.8151 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8096 -3.2916 2.5738 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2059 1.4256 -1.3076 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3434 -0.4096 -2.3914 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0926 4.8076 -2.9921 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0153 -3.2551 1.1472 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1856 -1.9459 2.4161 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0468 -1.7655 1.0604 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 17 20 1 0 13 21 1 0 21 22 1 0 22 23 2 0 21 24 1 0 9 25 1 0 2 26 1 0 11 5 1 0 19 14 1 0 22 10 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 0 4 31 1 0 4 32 1 0 7 33 1 0 8 34 1 0 13 35 1 1 15 36 1 0 16 37 1 0 18 38 1 0 19 39 1 0 20 40 1 0 21 41 1 1 24 42 1 0 25 43 1 0 26 44 1 0 26 45 1 0 26 46 1 0 M END

Standard InCHIKey	IPWPEUJWMOPJDG-OALUTQOASA-N
Standard InCHI	InChI=1S/C20H20O6/c1-10(2)3-8-13-14(22)9-15(23)16-17(24)18(25)19(26-20(13)16)11-4-6-12(21)7-5-11/h3-7,9,18-19,21-23,25H,8H2,1-2H3/t18-,19-/m0/s1
SMILES	CC(=CCc1c(O)cc(c2c1O[C@@H](c1ccc(cc1)O)[C@H](C2=O)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	356.13	Volume:	360.456 ? Van der Waals volume.
Dense:	0.988	LogP:	2.653 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.583 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.223 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	19.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.63	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.566	Fsp³:	0.25
MCE-18:	63.2 ? 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:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.668	Fluc inhibitor:	0.549 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.587 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.536 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.287	Promiscuous compounds:	0.162

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.427	MDCK Permeability:	-4.798
Pgp-inhibitor:	0.913	Pgp-substrate:	0.339
PAMPA:	0.439 ? 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):	0.001
20% Bioavailability (F20%):	0.696	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.912
Plasma Protein Binding (PPB):	94.527%	Volume Distribution (VD):	0.391
Fu:	5.377% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.991
BSEP inhibitor:	0.858

ADMET: Metabolism

CYP1A2-inhibitor:	0.124	CYP1A2-substrate:	0.995
CYP2C19-inhibitor:	0.473	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.309	CYP2C9-substrate:	0.136
CYP2D6-inhibitor:	0.751	CYP2D6-substrate:	0.975
CYP3A4-inhibitor:	0.01	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

6.259

Half-life (T1/2):

1.871

ADMET: Toxicity

hERG Blockers:	0.035	hERG Blockers (10um):	0.535
Human Hepatotoxicity (H-HT):	0.852	Drug-induced Liver Injury (DILI):	0.32
AMES Toxicity:	0.825	Rat Oral Acute Toxicity:	0.768
Maximum Recommended Daily Dose:	0.554	Skin Sensitization:	0.965
Carcinogencity:	0.194	Eye Corrosion:	0.001
Eye Irritation:	0.975	Respiratory Toxicity:	0.879
Drug-induced Neurotoxicity:	0.337	Ototoxicity:	0.736
Hematotoxicity:	0.141	Drug-induced Nephrotoxicity:	0.869
Genotoxicity:	0.994	RPMI-8226 Immunitoxicity:	0.099
A549 Cytotoxicity:	0.284	Hek293 Cytotoxicity:	0.724
BCF:	1.634 ? 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:	4.466 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.66 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.127 ? 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
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[14510598]
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24476.1	Phellodendron amurense var. wilsonii	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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
Inhibition	1

Activity Type	# Activity
Others	1

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
NPT1	Others	Radical scavenging activity	n.a.	Inhibition	=	20.9	%	PMID[14510598]

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 NPC262038 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	11759
0.1-0.2	31393
0.2-0.3	5856
0.3-0.4	657
0.4-0.5	141
0.5-0.6	29
0.6-0.7	10
0.7-0.8	0
0.8-0.85	1
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	NPC319910
0.8103	Intermediate Similarity	NPC278476
0.7458	Intermediate Similarity	NPC254412
0.6923	Remote Similarity	NPC488440
0.6885	Remote Similarity	NPC35567
0.6557	Remote Similarity	NPC107572
0.6557	Remote Similarity	NPC32739
0.6462	Remote Similarity	NPC211107
0.6349	Remote Similarity	NPC243171
0.6349	Remote Similarity	NPC482705
0.6333	Remote Similarity	NPC244250
0.6212	Remote Similarity	NPC138288
0.6087	Remote Similarity	NPC216035
0.5946	Remote Similarity	NPC259834
0.5942	Remote Similarity	NPC48579
0.5909	Remote Similarity	NPC293286
0.5781	Remote Similarity	NPC324436
0.5781	Remote Similarity	NPC78
0.5763	Remote Similarity	NPC62290
0.5763	Remote Similarity	NPC142731
0.5763	Remote Similarity	NPC326506
0.5714	Remote Similarity	NPC477244
0.5606	Remote Similarity	NPC66515
0.5571	Remote Similarity	NPC166934
0.5571	Remote Similarity	NPC63438
0.5522	Remote Similarity	NPC217706
0.5493	Remote Similarity	NPC180301
0.5455	Remote Similarity	NPC28918
0.5385	Remote Similarity	NPC76372
0.5385	Remote Similarity	NPC37496
0.5342	Remote Similarity	NPC262039
0.5303	Remote Similarity	NPC306829
0.527	Remote Similarity	NPC186847
0.5224	Remote Similarity	NPC171651
0.5224	Remote Similarity	NPC148757
0.5156	Remote Similarity	NPC246648
0.5152	Remote Similarity	NPC164980
0.5143	Remote Similarity	NPC161506
0.5079	Remote Similarity	NPC176869
0.5079	Remote Similarity	NPC3779
0.507	Remote Similarity	NPC610035
0.5068	Remote Similarity	NPC248793

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC262038 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3121
0.1-0.2	5832
0.2-0.3	190
0.3-0.4	7
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