NPASS Compound

Natural Product: NPC488409

Natural Product ID	NPC488409
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DYTUXVASBMSBTN-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101792026
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0001286] Benzenediols [CHEMONTID:0000137] Resorcinols

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 53 53 0 0 0 0 0 0 0 0999 V2000 5.5322 -0.3328 -2.0928 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6533 0.7948 -1.5438 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9284 1.0620 -0.1309 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8264 0.0807 0.9345 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6515 -0.6365 1.3647 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8795 -1.6458 0.6700 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2045 -1.3567 -0.6202 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2746 -0.1866 -0.5342 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1769 -0.4153 0.4884 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7205 0.8260 0.5069 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8249 0.6705 1.4930 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7006 1.8791 1.5047 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3625 2.0722 0.1810 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2408 0.8936 -0.1331 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5677 0.9344 0.3101 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4708 -0.0745 0.0850 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0487 -1.1948 -0.6184 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7467 -1.2528 -1.0624 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8390 -0.2119 -0.8227 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3033 -2.3572 -1.7646 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1879 -2.5064 -0.9220 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -7.7936 0.0120 0.5501 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3286 -0.4369 -3.1773 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5815 0.0210 -1.9889 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3291 -1.2637 -1.5401 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0756 1.7144 -2.1115 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6251 0.7752 -1.8875 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9821 1.5428 -0.1011 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2947 1.9658 0.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7023 -0.6890 0.8506 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2060 0.6367 1.9008 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9213 0.1982 1.7793 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9373 -1.1361 2.3795 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5384 -2.5770 0.5315 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0779 -2.1081 1.3767 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9003 -1.2971 -1.4425 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5619 -2.2941 -0.9006 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8669 0.0363 -1.5267 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8630 0.7003 -0.2217 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4000 -1.3306 0.2501 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6096 -0.5442 1.5005 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0750 1.6706 0.8438 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0094 1.0390 -0.5237 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4148 0.5579 2.5391 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4105 -0.2713 1.3415 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1221 2.8157 1.7157 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4490 1.8435 2.3394 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9856 3.0124 0.1595 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6357 2.1792 -0.6186 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8881 1.8083 0.8560 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8274 -0.2746 -1.1797 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6202 -2.4354 -2.7347 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8836 -0.1164 1.5694 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 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 18 19 2 0 18 20 1 0 17 21 1 0 16 22 1 0 19 14 1 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 2 27 1 0 3 28 1 0 3 29 1 0 4 30 1 0 4 31 1 0 5 32 1 0 5 33 1 0 6 34 1 0 6 35 1 0 7 36 1 0 7 37 1 0 8 38 1 0 8 39 1 0 9 40 1 0 9 41 1 0 10 42 1 0 10 43 1 0 11 44 1 0 11 45 1 0 12 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 15 50 1 0 19 51 1 0 20 52 1 0 22 53 1 0 M END

Standard InCHIKey	DYTUXVASBMSBTN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C19H31ClO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-14-17(21)19(20)18(22)15-16/h14-15,21-22H,2-13H2,1H3
SMILES	CCCCCCCCCCCCCc1cc(c(c(c1)O)Cl)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	326.2	Volume:	353.506 ? Van der Waals volume.
Dense:	0.923	LogP:	7.714 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.474 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.382 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	6.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.424	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.154	Fsp³:	0.684
MCE-18:	7.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.909	Fluc inhibitor:	0.331 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.166 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.906	Promiscuous compounds:	0.028

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.051	MDCK Permeability:	-4.77
Pgp-inhibitor:	0.002	Pgp-substrate:	0.007
PAMPA:	0.01 ? 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):	0.067
20% Bioavailability (F20%):	0.936	30% Bioavailability (F30%):	0.98
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.038	MRP1:	0.795
Plasma Protein Binding (PPB):	99.98%	Volume Distribution (VD):	1.438
Fu:	0.774% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.972
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.667
BSEP inhibitor:	0.614

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.772
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.989
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.018
CYP2D6-inhibitor:	0.803	CYP2D6-substrate:	0.043
CYP3A4-inhibitor:	0.854	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	1.0
HLM stability:	0.818 ? 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):

5.277

Half-life (T1/2):

0.552

ADMET: Toxicity

hERG Blockers:	0.594	hERG Blockers (10um):	0.905
Human Hepatotoxicity (H-HT):	0.463	Drug-induced Liver Injury (DILI):	0.591
AMES Toxicity:	0.058	Rat Oral Acute Toxicity:	0.401
Maximum Recommended Daily Dose:	0.554	Skin Sensitization:	0.99
Carcinogencity:	0.282	Eye Corrosion:	0.979
Eye Irritation:	0.996	Respiratory Toxicity:	0.984
Drug-induced Neurotoxicity:	0.093	Ototoxicity:	0.239
Hematotoxicity:	0.126	Drug-induced Nephrotoxicity:	0.132
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.051
A549 Cytotoxicity:	0.934	Hek293 Cytotoxicity:	0.496
BCF:	1.061 ? 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:	4.87 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.012 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.917 ? 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
NPO41023	Dictyostelium monochasioides	Species	n.a.	Eukaryota	Fruiting Bodies	n.a.	n.a.	PMID[28921976]
NPO41023	Dictyostelium monochasioides	Species	n.a.	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

Activity Type	# Activity
IC50	1
Inhibition	1

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
NPT15	Cell line	Jurkat	Homo sapiens	IC50	=	16000.0	nM	PMID[28921976]
NPT15	Cell line	Jurkat	Homo sapiens	Inhibition	<	50.0	%	PMID[28921976]

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 NPC488409 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	27615
0.1-0.2	20500
0.2-0.3	1515
0.3-0.4	135
0.4-0.5	58
0.5-0.6	20
0.6-0.7	8
0.7-0.8	0
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC488411
1.0	High Similarity	NPC488410
0.8286	Intermediate Similarity	NPC488413
0.8286	Intermediate Similarity	NPC488415
0.8286	Intermediate Similarity	NPC488414
0.8286	Intermediate Similarity	NPC488412
0.7105	Intermediate Similarity	NPC488416
0.6471	Remote Similarity	NPC294186
0.6471	Remote Similarity	NPC147310
0.6471	Remote Similarity	NPC137415
0.6471	Remote Similarity	NPC166313
0.6471	Remote Similarity	NPC192032
0.6471	Remote Similarity	NPC24407
0.6471	Remote Similarity	NPC11280
0.6286	Remote Similarity	NPC59506
0.5833	Remote Similarity	NPC37802
0.5588	Remote Similarity	NPC246056
0.5556	Remote Similarity	NPC123273
0.5556	Remote Similarity	NPC318325
0.5526	Remote Similarity	NPC3358
0.5526	Remote Similarity	NPC306884
0.5526	Remote Similarity	NPC603092
0.55	Remote Similarity	NPC146798
0.55	Remote Similarity	NPC222522
0.55	Remote Similarity	NPC106396
0.55	Remote Similarity	NPC94351
0.55	Remote Similarity	NPC168303
0.5405	Remote Similarity	NPC244513
0.5366	Remote Similarity	NPC232523
0.5366	Remote Similarity	NPC486908
0.525	Remote Similarity	NPC53051
0.525	Remote Similarity	NPC24404
0.525	Remote Similarity	NPC313030
0.5116	Remote Similarity	NPC71002
0.5116	Remote Similarity	NPC249828

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488409 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4011
0.1-0.2	4910
0.2-0.3	216
0.3-0.4	10
0.4-0.5	3
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