NPASS Compound

Natural Product: NPC560676

Natural Product ID	NPC560676
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-2-(4-hydroxyphenyl)-8,8-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4-one
IUPAC Name	(2~{S})-2-(4-hydroxyphenyl)-8,8-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0003520] Pyranoflavonoids

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 42 45 0 0 0 0 0 0 0 0999 V2000 4.1656 2.4205 -0.8242 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7171 1.0294 -1.2201 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8294 0.4447 -2.0762 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4339 1.0556 -1.9594 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3290 0.4393 -1.5729 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3666 -0.3247 -0.3289 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5217 -0.3989 0.4175 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5331 -1.1324 1.5983 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4233 -1.7963 2.0584 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2631 -1.7238 1.3119 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2395 -1.0061 0.1498 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9142 -0.9332 -0.5936 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1592 -1.5225 -0.2253 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0378 -0.4606 0.2241 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1352 0.7061 -0.5276 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9510 1.7522 -0.1512 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6867 1.6219 1.0093 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5239 2.6533 1.4279 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6290 0.4889 1.7926 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7856 -0.5479 1.3692 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9769 -2.6860 0.6942 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9615 -2.4044 1.7368 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1151 -2.7210 2.9305 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6388 0.2668 -0.0415 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2406 2.3484 -0.5554 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0199 3.1340 -1.6542 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5464 2.8038 0.0243 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4253 -0.2341 -2.8270 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4012 1.2523 -2.5841 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5355 -0.0872 -1.4243 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4123 1.6233 -2.8802 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4335 0.4951 -2.1487 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4666 -1.1518 2.1366 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4211 -2.3607 2.9620 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5755 -1.9319 -1.1824 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5473 0.7932 -1.4419 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0400 2.6624 -0.7188 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0344 3.1533 0.7174 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1889 0.3549 2.7024 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7073 -1.4522 1.9514 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8497 -3.0833 1.1838 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5444 -3.5406 0.0872 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 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 17 19 1 0 19 20 2 0 13 21 1 0 21 22 1 0 22 23 2 0 7 24 1 0 24 2 1 0 11 6 1 0 20 14 1 0 22 10 1 0 1 25 1 0 1 26 1 0 1 27 1 0 3 28 1 0 3 29 1 0 3 30 1 0 4 31 1 0 5 32 1 0 8 33 1 0 9 34 1 0 13 35 1 6 15 36 1 0 16 37 1 0 18 38 1 0 19 39 1 0 20 40 1 0 21 41 1 0 21 42 1 0 M END

Standard InCHIKey	AXHFLNLBMFDETO-SFHVURJKSA-N
Standard InCHI	InChI=1S/C20H18O4/c1-20(2)10-9-15-17(24-20)8-7-14-16(22)11-18(23-19(14)15)12-3-5-13(21)6-4-12/h3-10,18,21H,11H2,1-2H3/t18-/m0/s1
SMILES	CC1(C)C=CC2=C(C=CC3=C2O[C@H](C2=CC=C(O)C=C2)CC3=O)O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	322.12	Volume:	334.32 ? Van der Waals volume.
Dense:	0.964	LogP:	3.924 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.568 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.596 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	23.0
TPSA:	55.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.851	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.219	Fsp³:	0.25
MCE-18:	74.52 ? 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:	0.817	Fluc inhibitor:	0.584 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.578 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.589 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.413	Promiscuous compounds:	0.085

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.841	MDCK Permeability:	-4.71
Pgp-inhibitor:	0.943	Pgp-substrate:	0.187
PAMPA:	0.111 ? 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):	0.0
20% Bioavailability (F20%):	0.01	30% Bioavailability (F30%):	0.512
50% Bioavailability (F50%):	0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.623
Plasma Protein Binding (PPB):	97.833%	Volume Distribution (VD):	0.105
Fu:	1.962% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.347
OATP1B3 inhibitor:	0.944	BCRP inhibitor:	0.994
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.99
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.155	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.443
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.844 ? 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):

7.863

Half-life (T1/2):

0.938

ADMET: Toxicity

hERG Blockers:	0.306	hERG Blockers (10um):	0.563
Human Hepatotoxicity (H-HT):	0.797	Drug-induced Liver Injury (DILI):	0.618
AMES Toxicity:	0.723	Rat Oral Acute Toxicity:	0.792
Maximum Recommended Daily Dose:	0.773	Skin Sensitization:	0.874
Carcinogencity:	0.598	Eye Corrosion:	0.024
Eye Irritation:	0.96	Respiratory Toxicity:	0.905
Drug-induced Neurotoxicity:	0.929	Ototoxicity:	0.438
Hematotoxicity:	0.222	Drug-induced Nephrotoxicity:	0.698
Genotoxicity:	0.838	RPMI-8226 Immunitoxicity:	0.085
A549 Cytotoxicity:	0.447	Hek293 Cytotoxicity:	0.596
BCF:	1.626 ? 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:	4.407 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.764 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.263 ? 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
NPO54736	Dorstenia poinsettifolia	Genus	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5143	Millettia ferruginea	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5143	Millettia ferruginea	Species	Fabaceae	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

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

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 NPC560676 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	21080
0.1-0.2	24412
0.2-0.3	3643
0.3-0.4	532
0.4-0.5	144
0.5-0.6	34
0.6-0.7	5
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
0.7963	Intermediate Similarity	NPC472409
0.7419	Intermediate Similarity	NPC39752
0.7241	Intermediate Similarity	NPC59522
0.6949	Remote Similarity	NPC149796
0.6667	Remote Similarity	NPC34376
0.6452	Remote Similarity	NPC176229
0.6154	Remote Similarity	NPC23728
0.6119	Remote Similarity	NPC246948
0.597	Remote Similarity	NPC301276
0.5968	Remote Similarity	NPC11566
0.5873	Remote Similarity	NPC608647
0.5714	Remote Similarity	NPC475052
0.5714	Remote Similarity	NPC479206
0.5694	Remote Similarity	NPC101793
0.5652	Remote Similarity	NPC142405
0.5634	Remote Similarity	NPC479220
0.5634	Remote Similarity	NPC479207
0.5634	Remote Similarity	NPC488428
0.5634	Remote Similarity	NPC488427
0.5556	Remote Similarity	NPC479218
0.5556	Remote Similarity	NPC147145
0.5493	Remote Similarity	NPC479209
0.5484	Remote Similarity	NPC52576
0.5479	Remote Similarity	NPC479208
0.5469	Remote Similarity	NPC164980
0.5455	Remote Similarity	NPC142595
0.5439	Remote Similarity	NPC329225
0.5439	Remote Similarity	NPC147686
0.5417	Remote Similarity	NPC57313
0.5417	Remote Similarity	NPC479221
0.5373	Remote Similarity	NPC217706
0.5342	Remote Similarity	NPC479216
0.5342	Remote Similarity	NPC479219
0.5333	Remote Similarity	NPC483810
0.527	Remote Similarity	NPC160821
0.527	Remote Similarity	NPC110303
0.527	Remote Similarity	NPC601247
0.52	Remote Similarity	NPC132592
0.5195	Remote Similarity	NPC488431
0.5195	Remote Similarity	NPC488432
0.5143	Remote Similarity	NPC312973
0.5075	Remote Similarity	NPC75049

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC560676 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3824
0.1-0.2	5188
0.2-0.3	129
0.3-0.4	6
0.4-0.5	2
0.5-0.6	1
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
0.5439	Remote Similarity	NPD1549	Phase 2

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