NPASS Compound

Natural Product: NPC203491

Natural Product ID	NPC203491
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NOGPWNDHSHIXIK-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	15292596
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0002817] Dibenzopyrans [CHEMONTID:0000200] Xanthenes [CHEMONTID:0000204] Xanthones [CHEMONTID:0003518] 4-prenylated xanthones

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 62 66 0 0 0 0 0 0 0 0999 V2000 -4.2472 2.2637 2.1218 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4043 2.7188 0.9947 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2994 2.1054 0.6468 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8083 0.9078 1.3527 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6218 -0.2501 0.4132 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6460 -1.0001 -0.0799 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4604 -2.0704 -0.9520 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6095 -2.8158 -1.4339 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8455 -2.5287 -1.0845 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0930 -1.3993 -0.1609 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8846 -1.9904 1.0161 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9627 -0.3940 -0.9046 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9536 -0.7370 0.2637 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1851 -2.3837 -1.3320 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1392 -1.6294 -0.8378 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1387 -1.9606 -1.2332 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3444 -2.9268 -2.0243 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1837 -1.2031 -0.7370 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4903 -1.4718 -1.0859 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5564 -0.7223 -0.5989 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9313 -1.0119 -0.9773 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9553 -0.3076 -0.5273 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7496 0.8165 0.3885 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2656 2.0723 -0.3242 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5348 0.5806 1.6631 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4146 1.0539 0.7289 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3270 0.3311 0.2646 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0236 0.6031 0.6160 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9528 -0.1525 0.1241 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7095 0.1087 0.4603 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3157 -0.5691 0.0252 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7892 1.6646 1.4865 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9732 -3.4353 -2.1920 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8570 3.9278 0.2467 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4556 1.1857 2.0974 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7511 2.4849 3.1146 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2222 2.8158 2.1510 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6998 2.4691 -0.1892 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5301 0.5747 2.1188 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8385 1.1864 1.8207 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4391 -3.6493 -2.1153 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6909 -3.1261 -1.4766 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4319 -2.9965 1.2534 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9396 -2.1682 0.7499 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7470 -1.3789 1.9263 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5847 0.1814 -0.1802 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5661 -0.9549 -1.6352 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2737 0.2674 -1.4740 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6619 -2.2982 -1.7618 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1029 -1.8360 -1.6523 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9421 -0.5570 -0.8318 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4607 2.3640 -1.0330 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2130 1.8527 -0.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3502 2.8523 0.4384 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6299 0.6460 1.4434 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3298 1.3541 2.4232 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3125 -0.4245 2.0378 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7781 2.6077 1.0723 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6622 -4.3252 -1.8356 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8749 3.7575 -0.1824 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9660 4.7904 0.9424 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1684 4.1300 -0.5951 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 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 10 12 1 0 10 13 1 0 7 14 2 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 23 25 1 0 23 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 28 32 1 0 14 33 1 0 2 34 1 0 31 5 1 0 13 6 1 0 31 15 2 0 29 18 1 0 27 20 2 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 4 39 1 0 4 40 1 0 8 41 1 0 9 42 1 0 11 43 1 0 11 44 1 0 11 45 1 0 12 46 1 0 12 47 1 0 12 48 1 0 19 49 1 0 21 50 1 0 22 51 1 0 24 52 1 0 24 53 1 0 24 54 1 0 25 55 1 0 25 56 1 0 25 57 1 0 32 58 1 0 33 59 1 0 34 60 1 0 34 61 1 0 34 62 1 0 M END

Standard InCHIKey	NOGPWNDHSHIXIK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C28H28O6/c1-14(2)7-8-17-24-16(10-12-28(5,6)34-24)20(29)19-21(30)18-13-15-9-11-27(3,4)33-23(15)22(31)26(18)32-25(17)19/h7,9-13,29,31H,8H2,1-6H3
SMILES	CC(=CCc1c2c(C=CC(C)(C)O2)c(c2c(=O)c3cc4C=CC(C)(C)Oc4c(c3oc12)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	460.19	Volume:	476.439 ? Van der Waals volume.
Dense:	0.966	LogP:	5.816 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.151 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.818 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	28.0
TPSA:	89.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.348	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.713	Fsp³:	0.321
MCE-18:	71.676 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.979	Fluc inhibitor:	0.354 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.73 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.776 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.233	Promiscuous compounds:	0.285

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.029	MDCK Permeability:	-4.712
Pgp-inhibitor:	0.986	Pgp-substrate:	0.005
PAMPA:	0.395 ? 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):	0.005
20% Bioavailability (F20%):	0.848	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.573	MRP1:	0.974
Plasma Protein Binding (PPB):	95.956%	Volume Distribution (VD):	0.196
Fu:	3.763% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.894	BCRP inhibitor:	0.936
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.036
CYP3A4-inhibitor:	0.959	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.001	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):

2.053

Half-life (T1/2):

1.481

ADMET: Toxicity

hERG Blockers:	0.08	hERG Blockers (10um):	0.52
Human Hepatotoxicity (H-HT):	0.612	Drug-induced Liver Injury (DILI):	0.82
AMES Toxicity:	0.729	Rat Oral Acute Toxicity:	0.893
Maximum Recommended Daily Dose:	0.776	Skin Sensitization:	0.879
Carcinogencity:	0.843	Eye Corrosion:	0.0
Eye Irritation:	0.236	Respiratory Toxicity:	0.93
Drug-induced Neurotoxicity:	0.212	Ototoxicity:	0.434
Hematotoxicity:	0.309	Drug-induced Nephrotoxicity:	0.416
Genotoxicity:	0.779	RPMI-8226 Immunitoxicity:	0.09
A549 Cytotoxicity:	0.164	Hek293 Cytotoxicity:	0.482
BCF:	2.115 ? 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:	5.231 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.669 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	7.036 ? 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
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15678383]
NPO2110	Calophyllum blancoi	Species	Calophyllaceae	Eukaryota	n.a.	root	n.a.	PMID[15684529]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16045947]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	stem	n.a.	PMID[20188156]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	Malaysian	n.a.	PMID[7506311]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2110	Calophyllum blancoi	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2110	Calophyllum blancoi	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2804	Calophyllum inophyllum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2110	Calophyllum blancoi	Species	Calophyllaceae	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 NPC203491 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	25013
0.1-0.2	22468
0.2-0.3	1974
0.3-0.4	313
0.4-0.5	64
0.5-0.6	20
0.6-0.7	4
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
0.7183	Intermediate Similarity	NPC29876
0.7083	Intermediate Similarity	NPC103238
0.7083	Intermediate Similarity	NPC603436
0.6757	Remote Similarity	NPC218313
0.6667	Remote Similarity	NPC204879
0.6667	Remote Similarity	NPC16492
0.6053	Remote Similarity	NPC606144
0.5946	Remote Similarity	NPC133970
0.5921	Remote Similarity	NPC603548
0.5769	Remote Similarity	NPC23298
0.5769	Remote Similarity	NPC234644
0.56	Remote Similarity	NPC608878
0.5556	Remote Similarity	NPC288813
0.55	Remote Similarity	NPC167678
0.5488	Remote Similarity	NPC201829
0.5443	Remote Similarity	NPC237635
0.5375	Remote Similarity	NPC214236
0.5375	Remote Similarity	NPC220418
0.5309	Remote Similarity	NPC170026
0.5309	Remote Similarity	NPC14001
0.5301	Remote Similarity	NPC200625
0.5263	Remote Similarity	NPC488812
0.5244	Remote Similarity	NPC244407
0.5244	Remote Similarity	NPC83922
0.5185	Remote Similarity	NPC188433
0.5185	Remote Similarity	NPC204290
0.5059	Remote Similarity	NPC218871

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC203491 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4424
0.1-0.2	4695
0.2-0.3	30
0.3-0.4	1
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