NPASS Compound

Natural Product: NPC488724

Natural Product ID	NPC488724
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IFUJKMRKVLZNDU-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
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

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 69 73 0 0 0 0 0 0 0 0999 V2000 -4.5111 -0.2629 -3.0095 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9842 -0.4949 -1.8272 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7799 0.3036 -1.3803 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5700 -0.1665 -2.1409 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0178 1.7557 -1.8065 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6464 0.2133 0.0858 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7339 0.6877 0.8415 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7200 0.6480 2.2070 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5985 0.1249 2.8177 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5245 -0.3438 2.0960 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3438 -0.8843 2.7449 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2966 -0.9374 3.9979 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7752 -1.3604 1.9470 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8462 -1.9126 2.5112 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9763 -2.1188 1.5172 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3601 -3.1749 0.5759 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2955 -2.4892 -0.2349 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9429 -1.9202 -1.4764 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3511 -2.4612 -1.7034 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1747 -2.2896 -2.7230 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0944 -0.5506 -1.3001 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9602 -0.3035 0.0585 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6432 1.1324 0.2834 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7755 1.9293 -0.2794 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5043 2.7626 0.4145 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2445 2.9797 1.8590 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6107 3.5070 -0.2429 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0948 -0.8039 0.8528 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1044 -0.1777 0.9739 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7889 -1.2379 0.4556 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4332 -0.7855 -0.0111 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5175 -0.3126 0.6970 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5174 0.0539 4.2011 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8198 1.1973 0.1276 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9619 1.6996 0.7535 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3703 -0.8171 -3.3545 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0910 0.4881 -3.6552 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4027 -1.2442 -1.1816 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3931 -1.2459 -2.0292 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7008 0.4578 -1.9046 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7308 -0.0148 -3.2564 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7279 2.3840 -0.9395 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3942 2.0292 -2.6851 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0866 1.8976 -1.9731 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5609 1.0155 2.7608 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9276 -2.1866 3.5333 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8800 -2.4766 1.9996 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1516 -3.6644 0.0313 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8639 -3.9361 1.2140 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4541 -3.1655 -0.4892 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3708 -3.5223 -1.9710 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7108 -1.9331 -2.6404 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0578 -2.1389 -0.9285 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2628 -2.8790 -2.4984 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8389 -1.3269 -3.1817 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8405 -2.7873 -3.4373 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7575 1.4107 -0.3010 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5048 1.3730 1.3698 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9654 1.7695 -1.3412 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6081 2.0984 2.4125 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7835 3.9158 2.1910 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1659 3.1684 2.0642 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8899 3.0266 -1.2204 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3755 4.5677 -0.4214 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5095 3.3797 0.4056 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3057 0.8850 4.7621 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5659 2.2414 -0.0048 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6297 2.3688 1.5760 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5257 0.8551 1.2107 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 3 5 1 0 3 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 18 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 3 25 26 1 0 25 27 1 0 22 28 1 0 28 29 2 0 22 30 1 0 30 31 1 0 31 32 1 0 9 33 1 0 7 34 1 0 34 35 1 0 32 6 2 0 32 10 1 0 30 13 1 0 28 15 1 0 30 17 1 0 1 36 1 0 1 37 1 0 2 38 1 0 4 39 1 0 4 40 1 0 4 41 1 0 5 42 1 0 5 43 1 0 5 44 1 0 8 45 1 0 14 46 1 0 15 47 1 0 16 48 1 0 16 49 1 0 17 50 1 0 19 51 1 0 19 52 1 0 19 53 1 0 20 54 1 0 20 55 1 0 20 56 1 0 23 57 1 0 23 58 1 0 24 59 1 0 26 60 1 0 26 61 1 0 26 62 1 0 27 63 1 0 27 64 1 0 27 65 1 0 33 66 1 0 35 67 1 0 35 68 1 0 35 69 1 0 M END

Standard InCHIKey	IFUJKMRKVLZNDU-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C29H34O6/c1-9-26(4,5)22-19(33-8)14-18(30)21-23(31)17-12-16-13-20-27(6,7)35-28(25(16)32,11-10-15(2)3)29(17,20)34-24(21)22/h9-10,12,14,16,20,30H,1,11,13H2,2-8H3
SMILES	C=CC(C)(C)c1c(cc(c2C(=O)C3=CC4CC5C(C)(C)OC(CC=C(C)C)(C4=O)C35Oc12)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	478.24	Volume:	499.007 ? Van der Waals volume.
Dense:	0.958	LogP:	5.458 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.049 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.39 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	26.0
TPSA:	82.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.584	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.226	Fsp³:	0.517
MCE-18:	162.364 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.49	Fluc inhibitor:	0.029 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.605 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.941 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.167	Promiscuous compounds:	0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.876	MDCK Permeability:	-4.792
Pgp-inhibitor:	0.898	Pgp-substrate:	0.001
PAMPA:	0.016 ? 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):	0.018
20% Bioavailability (F20%):	0.983	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.979
Plasma Protein Binding (PPB):	95.642%	Volume Distribution (VD):	0.198
Fu:	3.506% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.996
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.055	CYP1A2-substrate:	0.993
CYP2C19-inhibitor:	0.954	CYP2C19-substrate:	0.867
CYP2C9-inhibitor:	0.052	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.996
CYP3A4-inhibitor:	0.566	CYP3A4-substrate:	0.131
CYP2B6-substrate:	0.406	CYP2C8-inhibitor:	0.999
HLM stability:	0.999 ? 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):

6.084

Half-life (T1/2):

0.81

ADMET: Toxicity

hERG Blockers:	0.126	hERG Blockers (10um):	0.599
Human Hepatotoxicity (H-HT):	0.711	Drug-induced Liver Injury (DILI):	0.54
AMES Toxicity:	0.554	Rat Oral Acute Toxicity:	0.922
Maximum Recommended Daily Dose:	0.927	Skin Sensitization:	0.581
Carcinogencity:	0.421	Eye Corrosion:	0.0
Eye Irritation:	0.005	Respiratory Toxicity:	0.878
Drug-induced Neurotoxicity:	0.459	Ototoxicity:	0.809
Hematotoxicity:	0.341	Drug-induced Nephrotoxicity:	0.22
Genotoxicity:	0.989	RPMI-8226 Immunitoxicity:	0.173
A549 Cytotoxicity:	0.464	Hek293 Cytotoxicity:	0.75
BCF:	2.028 ? 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:	4.791 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.759 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.172 ? 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
NPO40521	Garcinia bracteata	Species	Clusiaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[29565129]

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
GI50	2

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
NPT111	Cell line	K562	Homo sapiens	GI50	=	800.0	nM	PMID[29565129]
NPT116	Cell line	HL-60	Homo sapiens	GI50	=	200.0	nM	PMID[29565129]

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 NPC488724 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	8930
0.1-0.2	38345
0.2-0.3	2485
0.3-0.4	44
0.4-0.5	25
0.5-0.6	11
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
0.7945	Intermediate Similarity	NPC193222
0.7838	Intermediate Similarity	NPC488712
0.7838	Intermediate Similarity	NPC475080
0.7838	Intermediate Similarity	NPC488719
0.7778	Intermediate Similarity	NPC476056
0.7778	Intermediate Similarity	NPC488723
0.7532	Intermediate Similarity	NPC488714
0.7532	Intermediate Similarity	NPC488713
0.7143	Intermediate Similarity	NPC608101
0.6986	Remote Similarity	NPC475107
0.6986	Remote Similarity	NPC43490
0.6986	Remote Similarity	NPC605777
0.6933	Remote Similarity	NPC94796
0.6933	Remote Similarity	NPC611777
0.6753	Remote Similarity	NPC607281
0.6471	Remote Similarity	NPC476255
0.6456	Remote Similarity	NPC479154
0.6329	Remote Similarity	NPC475109
0.5882	Remote Similarity	NPC131578
0.5882	Remote Similarity	NPC611483
0.5761	Remote Similarity	NPC610447
0.5747	Remote Similarity	NPC286422
0.5747	Remote Similarity	NPC603867
0.5732	Remote Similarity	NPC488722
0.5464	Remote Similarity	NPC601073
0.5464	Remote Similarity	NPC609328
0.5385	Remote Similarity	NPC223413
0.5294	Remote Similarity	NPC118128
0.5294	Remote Similarity	NPC488720

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488724 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3616
0.1-0.2	5496
0.2-0.3	38
0.3-0.4	0
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