NPASS Compound

Natural Product: NPC559434

Natural Product ID	NPC559434
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	10169-80-9
IUPAC Name	1,3,8-trihydroxy-2-methyl-anthracene-9,10-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 30 32 0 0 0 0 0 0 0 0999 V2000 4.3789 0.5456 -0.3693 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9898 -0.0188 -0.2637 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7795 -1.3840 -0.2483 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9159 -2.1907 -0.3353 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5204 -1.9295 -0.1526 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4156 -1.1094 -0.0681 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9505 -1.6172 0.0357 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1011 -2.8657 0.0466 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1055 -0.7534 0.1241 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3854 -1.2551 0.2214 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4553 -0.3798 0.3033 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2735 0.9935 0.2901 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9818 1.4695 0.1919 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8217 2.8491 0.1803 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8932 0.6095 0.1086 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5357 1.1342 0.0054 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4125 2.3908 -0.0034 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6283 0.2525 -0.0837 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8889 0.8003 -0.1795 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0277 2.1693 -0.1894 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8354 0.4134 0.6490 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3161 1.5958 -0.6533 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9209 -0.0228 -1.1487 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8663 -3.1931 -0.2805 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3661 -3.0090 -0.1414 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5675 -2.3172 0.2348 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4609 -0.7587 0.3797 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1319 1.6490 0.3557 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4930 3.2478 -0.7029 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7199 2.6841 -1.0209 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 3 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 19 2 1 0 18 6 1 0 15 9 1 0 1 21 1 0 1 22 1 0 1 23 1 0 4 24 1 0 5 25 1 0 10 26 1 0 11 27 1 0 12 28 1 0 14 29 1 0 20 30 1 0 M END

Standard InCHIKey	DKBPRYNCMDJTRD-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H10O5/c1-6-10(17)5-8-12(13(6)18)15(20)11-7(14(8)19)3-2-4-9(11)16/h2-5,16-18H,1H3
SMILES	CC1=C(O)C=C2C(=O)C3=CC=CC(O)=C3C(=O)C2=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	270.05	Volume:	265.186 ? Van der Waals volume.
Dense:	1.018	LogP:	3.694 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.08 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.173 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	18.0
TPSA:	94.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.579	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.395	Fsp³:	0.067
MCE-18:	38.0 ? 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:	0
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.521	Fluc inhibitor:	0.532 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.264 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.362 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.649	Promiscuous compounds:	0.239

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.043	MDCK Permeability:	-4.739
Pgp-inhibitor:	0.053	Pgp-substrate:	0.034
PAMPA:	0.985 ? 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):	0.229
20% Bioavailability (F20%):	0.088	30% Bioavailability (F30%):	0.571
50% Bioavailability (F50%):	0.937

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.788
Plasma Protein Binding (PPB):	95.353%	Volume Distribution (VD):	0.559
Fu:	6.209% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.974
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.021
BSEP inhibitor:	0.086

ADMET: Metabolism

CYP1A2-inhibitor:	0.997	CYP1A2-substrate:	0.301
CYP2C19-inhibitor:	0.083	CYP2C19-substrate:	0.014
CYP2C9-inhibitor:	0.011	CYP2C9-substrate:	0.01
CYP2D6-inhibitor:	0.016	CYP2D6-substrate:	0.04
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.309
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.768 ? 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):

5.242

Half-life (T1/2):

1.005

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.509
Human Hepatotoxicity (H-HT):	0.637	Drug-induced Liver Injury (DILI):	0.826
AMES Toxicity:	0.908	Rat Oral Acute Toxicity:	0.611
Maximum Recommended Daily Dose:	0.368	Skin Sensitization:	0.977
Carcinogencity:	0.713	Eye Corrosion:	0.002
Eye Irritation:	0.991	Respiratory Toxicity:	0.978
Drug-induced Neurotoxicity:	0.142	Ototoxicity:	0.358
Hematotoxicity:	0.652	Drug-induced Nephrotoxicity:	0.385
Genotoxicity:	0.906	RPMI-8226 Immunitoxicity:	0.343
A549 Cytotoxicity:	0.892	Hek293 Cytotoxicity:	0.639
BCF:	1.658 ? 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:	4.064 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.952 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.343 ? 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
NPO60995	Cassia alata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC559434 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	26883
0.1-0.2	20332
0.2-0.3	2305
0.3-0.4	236
0.4-0.5	72
0.5-0.6	20
0.6-0.7	7
0.7-0.8	1
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
0.7273	Intermediate Similarity	NPC103540
0.7222	Intermediate Similarity	NPC53206
0.7027	Intermediate Similarity	NPC604340
0.65	Remote Similarity	NPC282923
0.6471	Remote Similarity	NPC375356
0.6389	Remote Similarity	NPC300274
0.6389	Remote Similarity	NPC608834
0.6341	Remote Similarity	NPC205992
0.6136	Remote Similarity	NPC21599
0.6098	Remote Similarity	NPC53414
0.5952	Remote Similarity	NPC416
0.5854	Remote Similarity	NPC99731
0.5833	Remote Similarity	NPC169452
0.5814	Remote Similarity	NPC70622
0.5682	Remote Similarity	NPC487321
0.5625	Remote Similarity	NPC242994
0.56	Remote Similarity	NPC181560
0.5556	Remote Similarity	NPC257644
0.5435	Remote Similarity	NPC288089
0.5435	Remote Similarity	NPC604901
0.5435	Remote Similarity	NPC608971
0.5417	Remote Similarity	NPC66593
0.5319	Remote Similarity	NPC124365
0.525	Remote Similarity	NPC142956
0.5227	Remote Similarity	NPC199253
0.52	Remote Similarity	NPC193555
0.5192	Remote Similarity	NPC601296
0.5122	Remote Similarity	NPC73061
0.5098	Remote Similarity	NPC115458
0.5094	Remote Similarity	NPC606760

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC559434 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4411
0.1-0.2	4544
0.2-0.3	189
0.3-0.4	3
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7273	Intermediate Similarity	NPD1470	Phase 4

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