NPASS Compound

Natural Product: NPC603326

Natural Product ID	NPC603326
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JJJSFAGPWHEUBT-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL443859
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 26 26 0 0 0 0 0 0 0 0999 V2000 4.6118 -1.0559 0.8476 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7253 -0.3719 -0.0142 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3879 -0.1603 0.2714 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9208 -0.5933 1.3509 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5548 0.5587 -0.6859 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1566 0.7238 -0.2788 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1670 1.8566 0.4474 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4643 2.0874 0.8699 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4643 1.2101 0.5864 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7515 1.4852 1.0323 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1606 0.0734 -0.1376 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1977 -0.7995 -0.4104 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0483 -1.9944 -1.1335 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8545 -0.1631 -0.5654 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9915 -1.7029 1.5020 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3139 -1.6325 0.2212 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1342 -0.3245 1.4997 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0070 1.5690 -0.8759 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5526 -0.0231 -1.6472 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5699 2.6093 0.7176 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6909 2.9789 1.4352 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4913 1.7969 0.3984 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0677 -2.4526 -0.8276 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8130 -2.7540 -0.8426 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1358 -1.8723 -2.2247 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6193 -1.0490 -1.1295 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 3 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 1 0 11 14 2 0 14 6 1 0 1 15 1 0 1 16 1 0 1 17 1 0 5 18 1 0 5 19 1 0 7 20 1 0 8 21 1 0 10 22 1 0 13 23 1 0 13 24 1 0 13 25 1 0 14 26 1 0 M END

Standard InCHIKey	JJJSFAGPWHEUBT-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C10H12O4/c1-13-9-5-7(3-4-8(9)11)6-10(12)14-2/h3-5,11H,6H2,1-2H3
SMILES	COC(=O)Cc1ccc(O)c(OC)c1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	196.07	Volume:	197.575 ? Van der Waals volume.
Dense:	0.992	LogP:	1.19 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.279 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.31 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	7.0
TPSA:	55.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.736	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.718	Fsp³:	0.3
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:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.082	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.048 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.212 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.969	Promiscuous compounds:	0.24

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.757	MDCK Permeability:	-4.525
Pgp-inhibitor:	0.018	Pgp-substrate:	0.048
PAMPA:	0.225 ? 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%):	0.474	30% Bioavailability (F30%):	0.315
50% Bioavailability (F50%):	0.802

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.022	MRP1:	0.909
Plasma Protein Binding (PPB):	42.98%	Volume Distribution (VD):	-0.362
Fu:	51.502% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.781
OATP1B3 inhibitor:	0.97	BCRP inhibitor:	0.015
BSEP inhibitor:	0.516

ADMET: Metabolism

CYP1A2-inhibitor:	0.925	CYP1A2-substrate:	0.331
CYP2C19-inhibitor:	0.917	CYP2C19-substrate:	0.221
CYP2C9-inhibitor:	0.851	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.523	CYP2D6-substrate:	0.19
CYP3A4-inhibitor:	0.357	CYP3A4-substrate:	0.011
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.602
HLM stability:	0.875 ? 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):

8.423

Half-life (T1/2):

1.166

ADMET: Toxicity

hERG Blockers:	0.06	hERG Blockers (10um):	0.55
Human Hepatotoxicity (H-HT):	0.322	Drug-induced Liver Injury (DILI):	0.335
AMES Toxicity:	0.478	Rat Oral Acute Toxicity:	0.525
Maximum Recommended Daily Dose:	0.157	Skin Sensitization:	0.835
Carcinogencity:	0.431	Eye Corrosion:	0.576
Eye Irritation:	0.975	Respiratory Toxicity:	0.676
Drug-induced Neurotoxicity:	0.45	Ototoxicity:	0.159
Hematotoxicity:	0.253	Drug-induced Nephrotoxicity:	0.34
Genotoxicity:	0.203	RPMI-8226 Immunitoxicity:	0.038
A549 Cytotoxicity:	0.033	Hek293 Cytotoxicity:	0.107
BCF:	0.493 ? 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:	2.712 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.651 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.945 ? 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
NPO13933	Cerbera manghas	Species	Apocynaceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1248/cpb.25.2744]
NPO13933	Cerbera manghas	Species	Apocynaceae	Eukaryota	n.a.	seed	n.a.	DOI[10.1248/cpb.25.2744]
NPO13933	Cerbera manghas	Species	Apocynaceae	Eukaryota	n.a.	bark	n.a.	DOI[10.1248/cpb.25.2744]
NPO13933	Cerbera manghas	Species	Apocynaceae	Eukaryota	n.a.	seed	n.a.	PMID[15305009]
NPO7792	Coreopsis grandiflora	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13933	Cerbera manghas	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO56496	Macadamia integrifolia	Species	Proteaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13933	Cerbera manghas	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13933	Cerbera manghas	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7792	Coreopsis grandiflora	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13933	Cerbera manghas	Species	Apocynaceae	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

Activity Type	# Activity
Activity	2

Activity Type	# Activity
Organism	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

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	25.0	nmol	PMID[7119808]
NPT32	Organism	Mus musculus	Mus musculus	Activity	>	100.0	nmol	PMID[7119808]

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 NPC603326 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	19111
0.1-0.2	22901
0.2-0.3	6752
0.3-0.4	755
0.4-0.5	259
0.5-0.6	57
0.6-0.7	13
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
0.6829	Remote Similarity	NPC177291
0.6667	Remote Similarity	NPC156840
0.6316	Remote Similarity	NPC257124
0.6154	Remote Similarity	NPC8547
0.6154	Remote Similarity	NPC221049
0.6154	Remote Similarity	NPC140359
0.6047	Remote Similarity	NPC127937
0.6	Remote Similarity	NPC165133
0.6	Remote Similarity	NPC242885
0.6	Remote Similarity	NPC95614
0.6	Remote Similarity	NPC471693
0.6	Remote Similarity	NPC193544
0.6	Remote Similarity	NPC232316
0.5952	Remote Similarity	NPC299406
0.5854	Remote Similarity	NPC255675
0.5714	Remote Similarity	NPC57490
0.5714	Remote Similarity	NPC85488
0.5714	Remote Similarity	NPC603989
0.5682	Remote Similarity	NPC194416
0.5682	Remote Similarity	NPC31344
0.5682	Remote Similarity	NPC317769
0.5581	Remote Similarity	NPC197757
0.5581	Remote Similarity	NPC17943
0.5556	Remote Similarity	NPC66518
0.5532	Remote Similarity	NPC481914
0.551	Remote Similarity	NPC68779
0.551	Remote Similarity	NPC108598
0.551	Remote Similarity	NPC487680
0.5455	Remote Similarity	NPC107588
0.5455	Remote Similarity	NPC137537
0.5435	Remote Similarity	NPC51840
0.5435	Remote Similarity	NPC227217
0.5435	Remote Similarity	NPC117780
0.5417	Remote Similarity	NPC53305
0.5405	Remote Similarity	NPC7097
0.5385	Remote Similarity	NPC203719
0.5385	Remote Similarity	NPC293619
0.5366	Remote Similarity	NPC159418
0.5333	Remote Similarity	NPC203133
0.5333	Remote Similarity	NPC312675
0.5333	Remote Similarity	NPC262156
0.5333	Remote Similarity	NPC184651
0.5333	Remote Similarity	NPC113865
0.5306	Remote Similarity	NPC201777
0.5306	Remote Similarity	NPC604524
0.5263	Remote Similarity	NPC1065
0.525	Remote Similarity	NPC32163
0.525	Remote Similarity	NPC309203
0.525	Remote Similarity	NPC604189
0.5217	Remote Similarity	NPC117214
0.5217	Remote Similarity	NPC56214
0.5217	Remote Similarity	NPC487676
0.5217	Remote Similarity	NPC476968
0.5208	Remote Similarity	NPC5018
0.5208	Remote Similarity	NPC74817
0.5208	Remote Similarity	NPC607444
0.52	Remote Similarity	NPC137427
0.5192	Remote Similarity	NPC253481
0.5192	Remote Similarity	NPC253722
0.5192	Remote Similarity	NPC603813
0.5111	Remote Similarity	NPC184632
0.5106	Remote Similarity	NPC82679
0.5102	Remote Similarity	NPC114298
0.5102	Remote Similarity	NPC159968
0.5102	Remote Similarity	NPC103823
0.5098	Remote Similarity	NPC481913
0.5098	Remote Similarity	NPC163083
0.5094	Remote Similarity	NPC273657
0.5094	Remote Similarity	NPC610326
0.5091	Remote Similarity	NPC606339

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC603326 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2769
0.1-0.2	5778
0.2-0.3	576
0.3-0.4	24
0.4-0.5	2
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
0.6316	Remote Similarity	NPD228	Phase 0

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