NPASS Compound

Natural Product: NPC603612

Natural Product ID	NPC603612
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DHAZIUXMHRHVMP-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL206900
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 56 55 0 0 0 0 0 0 0 0999 V2000 7.4559 1.0082 -1.8328 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2672 1.4778 -1.0182 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0119 0.5013 0.0951 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8480 0.9085 0.9459 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5714 1.0008 0.1432 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4060 1.4092 1.0205 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1532 0.4434 2.1305 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8347 -0.9423 1.6630 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5680 -0.8601 0.7957 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1706 -2.1847 0.2844 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9792 -2.2114 -0.6264 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3171 -1.7612 -0.2600 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6064 -0.3604 0.0880 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1090 -0.2992 0.3633 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8171 -1.3290 0.2680 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7061 0.8809 0.7183 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0743 1.0308 0.9874 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9936 0.7253 -0.1535 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8078 1.5949 -1.3598 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4353 1.5027 -1.9582 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1348 0.4212 -1.1770 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1125 0.3330 -2.6327 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9741 1.8621 -2.2889 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4836 2.4693 -0.5981 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3893 1.4686 -1.7048 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7549 -0.4953 -0.3638 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9016 0.3547 0.7353 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7240 0.1840 1.7810 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9973 1.9183 1.4043 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4004 0.0829 -0.4174 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7275 1.8326 -0.6040 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7210 2.3792 1.5026 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5173 1.6658 0.4160 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9999 0.4800 2.8291 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2415 0.8155 2.6753 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5456 -1.5470 2.5468 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6508 -1.4545 1.1521 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2017 -0.5238 1.5495 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6264 -0.1223 0.0077 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0821 -2.5771 -0.2930 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0944 -2.9598 1.1062 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6767 -1.7208 -1.6382 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1215 -3.2957 -1.0167 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7225 -2.4735 0.5392 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0222 -2.0235 -1.1319 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 0.1051 0.9386 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4325 0.3409 -0.7838 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3796 0.5168 1.9280 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2162 2.1267 1.2120 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7551 -0.3243 -0.4998 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0543 0.6589 0.1662 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9667 2.6443 -1.0384 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5586 1.2711 -2.1116 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6472 1.9487 -1.3544 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4340 2.0624 -2.9310 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1841 0.4419 -2.1988 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 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 1 21 1 0 1 22 1 0 1 23 1 0 2 24 1 0 2 25 1 0 3 26 1 0 3 27 1 0 4 28 1 0 4 29 1 0 5 30 1 0 5 31 1 0 6 32 1 0 6 33 1 0 7 34 1 0 7 35 1 0 8 36 1 0 8 37 1 0 9 38 1 0 9 39 1 0 10 40 1 0 10 41 1 0 11 42 1 0 11 43 1 0 12 44 1 0 12 45 1 0 13 46 1 0 13 47 1 0 17 48 1 0 17 49 1 0 18 50 1 0 18 51 1 0 19 52 1 0 19 53 1 0 20 54 1 0 20 55 1 0 20 56 1 0 M END

Standard InCHIKey	DHAZIUXMHRHVMP-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H36O2/c1-3-5-7-8-9-10-11-12-13-14-15-16-18(19)20-17-6-4-2/h3-17H2,1-2H3
SMILES	CCCCCCCCCCCCCC(=O)OCCCC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	284.27	Volume:	334.828 ? Van der Waals volume.
Dense:	0.849	LogP:	7.114 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.303 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.686 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	1.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.271	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.805	Fsp³:	0.944
MCE-18:	0.0 ? 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:	0.112	Fluc inhibitor:	0.187 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.997	Promiscuous compounds:	0.344

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.042	MDCK Permeability:	-4.805
Pgp-inhibitor:	0.003	Pgp-substrate:	0.128
PAMPA:	0.003 ? 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):	0.402
20% Bioavailability (F20%):	0.881	30% Bioavailability (F30%):	0.903
50% Bioavailability (F50%):	0.859

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.097	MRP1:	0.989
Plasma Protein Binding (PPB):	99.124%	Volume Distribution (VD):	1.063
Fu:	1.085% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.091
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.64
BSEP inhibitor:	0.951

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.878
CYP2C9-inhibitor:	0.216	CYP2C9-substrate:	0.032
CYP2D6-inhibitor:	0.018	CYP2D6-substrate:	0.344
CYP3A4-inhibitor:	0.143	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.409	CYP2C8-inhibitor:	0.995
HLM stability:	0.106 ? 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):

5.613

Half-life (T1/2):

0.404

ADMET: Toxicity

hERG Blockers:	0.407	hERG Blockers (10um):	0.827
Human Hepatotoxicity (H-HT):	0.238	Drug-induced Liver Injury (DILI):	0.175
AMES Toxicity:	0.048	Rat Oral Acute Toxicity:	0.105
Maximum Recommended Daily Dose:	0.149	Skin Sensitization:	0.955
Carcinogencity:	0.386	Eye Corrosion:	0.987
Eye Irritation:	0.997	Respiratory Toxicity:	0.766
Drug-induced Neurotoxicity:	0.025	Ototoxicity:	0.105
Hematotoxicity:	0.098	Drug-induced Nephrotoxicity:	0.188
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.128	Hek293 Cytotoxicity:	0.061
BCF:	1.155 ? 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:	4.72 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.979 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.056 ? 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
NPO43135	Opuntia microdasys	Species	Cactaceae	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
MIC	3

Activity Type	# Activity
Organism	3

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
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	4365158.32	nM	PMID[16554156]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	2630267.99	nM	PMID[16554156]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	3548133.89	nM	PMID[16554156]

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
-	Rattus norvegicus	LD50	>	8000.0	mg/kg	ToxVal
-	Homo sapiens	PAC-3	=	1628.96	mg/m3	ToxVal
-	Homo sapiens	PAC-2	=	267.614	mg/m3	ToxVal
-	Homo sapiens	PAC-1	=	24.4343	mg/m3	ToxVal
-	Homo sapiens	MEG	=	100.0	mg/m3	ToxVal
-	Homo sapiens	MEG	=	600.0	mg/m3	ToxVal
-	Homo sapiens	MEG	=	3500.0	mg/m3	ToxVal

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 NPC603612 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	26085
0.1-0.2	21688
0.2-0.3	1767
0.3-0.4	198
0.4-0.5	54
0.5-0.6	39
0.6-0.7	8
0.7-0.8	1
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.88	High Similarity	NPC149299
0.84	Intermediate Similarity	NPC80396
0.84	Intermediate Similarity	NPC154642
0.8333	Intermediate Similarity	NPC476550
0.7931	Intermediate Similarity	NPC223677
0.7692	Intermediate Similarity	NPC80641
0.76	Intermediate Similarity	NPC223249
0.7308	Intermediate Similarity	NPC154396
0.7308	Intermediate Similarity	NPC286695
0.72	Intermediate Similarity	NPC250028
0.72	Intermediate Similarity	NPC236579
0.72	Intermediate Similarity	NPC80234
0.72	Intermediate Similarity	NPC203531
0.72	Intermediate Similarity	NPC256163
0.72	Intermediate Similarity	NPC40597
0.6923	Remote Similarity	NPC12904
0.6667	Remote Similarity	NPC163345
0.64	Remote Similarity	NPC53541
0.64	Remote Similarity	NPC166804
0.6296	Remote Similarity	NPC322892
0.6207	Remote Similarity	NPC310746
0.6129	Remote Similarity	NPC71761
0.6	Remote Similarity	NPC26253
0.5926	Remote Similarity	NPC86545
0.5926	Remote Similarity	NPC286498
0.5926	Remote Similarity	NPC223374
0.5926	Remote Similarity	NPC196442
0.5926	Remote Similarity	NPC301398
0.5926	Remote Similarity	NPC608162
0.5926	Remote Similarity	NPC609004
0.5862	Remote Similarity	NPC600941
0.5833	Remote Similarity	NPC99700
0.5806	Remote Similarity	NPC488257
0.5806	Remote Similarity	NPC469937
0.5806	Remote Similarity	NPC94699
0.5806	Remote Similarity	NPC128061
0.5806	Remote Similarity	NPC320588
0.5806	Remote Similarity	NPC53463
0.5769	Remote Similarity	NPC201622
0.5769	Remote Similarity	NPC305660
0.5769	Remote Similarity	NPC12156
0.5769	Remote Similarity	NPC161097
0.5769	Remote Similarity	NPC28598
0.5769	Remote Similarity	NPC326758
0.5769	Remote Similarity	NPC22903
0.5769	Remote Similarity	NPC54980
0.5667	Remote Similarity	NPC223675
0.5667	Remote Similarity	NPC68577
0.5652	Remote Similarity	NPC327450
0.5652	Remote Similarity	NPC234005
0.5625	Remote Similarity	NPC55678
0.56	Remote Similarity	NPC3693
0.56	Remote Similarity	NPC476549
0.5556	Remote Similarity	NPC40965
0.5385	Remote Similarity	NPC140229
0.5357	Remote Similarity	NPC81263
0.5357	Remote Similarity	NPC47363
0.5357	Remote Similarity	NPC287231
0.5357	Remote Similarity	NPC317128
0.5357	Remote Similarity	NPC178643
0.5294	Remote Similarity	NPC28779
0.5185	Remote Similarity	NPC248233

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC603612 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6717
0.1-0.2	2246
0.2-0.3	153
0.3-0.4	25
0.4-0.5	3
0.5-0.6	4
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
0.75	Intermediate Similarity	NPD900	Pre-clinical
0.5882	Remote Similarity	NPD631	Phase 4
0.5714	Remote Similarity	NPD630	Approved
0.5625	Remote Similarity	NPD6125	Phase 4
0.5357	Remote Similarity	NPD2699	Pre-clinical

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