NPASS Compound

Natural Product: NPC555104

Natural Product ID	NPC555104
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-Acetylchrysophanol
IUPAC Name	1-acetyl-4,5-dihydroxy-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 34 36 0 0 0 0 0 0 0 0999 V2000 -2.9566 -2.1388 0.1040 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4822 -1.0731 -0.7978 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6395 -1.1602 -2.0593 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8142 0.1250 -0.2946 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5071 1.2647 0.0504 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9926 1.2380 -0.1087 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8753 2.3938 0.5248 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5050 2.3481 0.6460 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1458 3.4765 1.1220 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1917 1.2090 0.3015 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4348 0.0690 -0.1763 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3025 -1.1392 -0.5418 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2923 -2.1587 -0.9726 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7505 -1.1266 -0.3915 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4953 -2.2500 -0.7254 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8682 -2.2770 -0.5972 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5564 -1.1771 -0.1277 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8077 -0.0631 0.2023 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4453 1.0619 0.6758 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4362 -0.0224 0.0792 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6493 1.1551 0.4285 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2214 2.2014 0.8668 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9308 -1.8257 0.5520 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0759 -3.0630 -0.5051 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2792 -2.3544 0.9381 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4023 0.5269 0.6317 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1954 0.8784 -1.1479 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3862 2.2707 0.0385 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4711 3.2660 0.7822 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1097 4.4251 0.8807 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9967 -3.1478 -1.1023 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4548 -3.1489 -0.8554 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6400 -1.2025 -0.0280 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3886 1.4188 1.6067 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 2 0 5 6 1 0 5 7 1 0 7 8 2 0 8 9 1 0 8 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 18 20 2 0 20 21 1 0 21 22 2 0 11 4 1 0 20 14 1 0 21 10 1 0 1 23 1 0 1 24 1 0 1 25 1 0 6 26 1 0 6 27 1 0 6 28 1 0 7 29 1 0 9 30 1 0 15 31 1 0 16 32 1 0 17 33 1 0 19 34 1 0 M END

Standard InCHIKey	UORBEWUEAVQISH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H12O5/c1-7-6-11(20)14-15(12(7)8(2)18)16(21)9-4-3-5-10(19)13(9)17(14)22/h3-6,19-20H,1-2H3
SMILES	CC(=O)C1=C(C)C=C(O)C2=C1C(=O)C1=CC=CC(O)=C1C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	296.07	Volume:	297.142 ? Van der Waals volume.
Dense:	0.996	LogP:	4.0 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.295 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-7.181 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	19.0
TPSA:	91.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.673	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.443	Fsp³:	0.118
MCE-18:	40.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.171	Fluc inhibitor:	0.115 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.225 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.511 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.409	Promiscuous compounds:	0.197

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.888	MDCK Permeability:	-4.795
Pgp-inhibitor:	0.681	Pgp-substrate:	0.197
PAMPA:	0.842 ? 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):	0.345
20% Bioavailability (F20%):	0.151	30% Bioavailability (F30%):	0.923
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.736
Plasma Protein Binding (PPB):	96.235%	Volume Distribution (VD):	0.446
Fu:	4.195% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.404
BSEP inhibitor:	0.343

ADMET: Metabolism

CYP1A2-inhibitor:	0.933	CYP1A2-substrate:	0.802
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.4
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.379
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.357
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	0.327
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.808 ? 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):

2.592

Half-life (T1/2):

1.22

ADMET: Toxicity

hERG Blockers:	0.042	hERG Blockers (10um):	0.532
Human Hepatotoxicity (H-HT):	0.66	Drug-induced Liver Injury (DILI):	0.983
AMES Toxicity:	0.944	Rat Oral Acute Toxicity:	0.45
Maximum Recommended Daily Dose:	0.237	Skin Sensitization:	0.961
Carcinogencity:	0.859	Eye Corrosion:	0.0
Eye Irritation:	0.968	Respiratory Toxicity:	0.902
Drug-induced Neurotoxicity:	0.328	Ototoxicity:	0.37
Hematotoxicity:	0.889	Drug-induced Nephrotoxicity:	0.67
Genotoxicity:	0.929	RPMI-8226 Immunitoxicity:	0.377
A549 Cytotoxicity:	0.94	Hek293 Cytotoxicity:	0.509
BCF:	1.527 ? 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:	4.024 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.948 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.434 ? 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
NPO45958	Streptomyces sp. GW6225	Genus	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO52616	Streptomyces sp. isolate GW6225	Genus	Streptomycetaceae	Bacteria	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 NPC555104 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	26793
0.1-0.2	20410
0.2-0.3	2379
0.3-0.4	204
0.4-0.5	55
0.5-0.6	13
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8	Intermediate Similarity	NPC487321
0.7	Intermediate Similarity	NPC99731
0.6216	Remote Similarity	NPC103540
0.6078	Remote Similarity	NPC13715
0.6047	Remote Similarity	NPC282923
0.5946	Remote Similarity	NPC375356
0.5909	Remote Similarity	NPC205992
0.5897	Remote Similarity	NPC608834
0.5849	Remote Similarity	NPC43188
0.5714	Remote Similarity	NPC604340
0.55	Remote Similarity	NPC300274
0.5435	Remote Similarity	NPC70622
0.5306	Remote Similarity	NPC124365
0.5217	Remote Similarity	NPC199253
0.5217	Remote Similarity	NPC416
0.5179	Remote Similarity	NPC606486
0.5102	Remote Similarity	NPC604901
0.5102	Remote Similarity	NPC608971

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC555104 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4535
0.1-0.2	4446
0.2-0.3	164
0.3-0.4	3
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
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
0.6216	Remote 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