NPASS Compound

Natural Product: NPC602429

Natural Product ID	NPC602429
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ROLSKNVQSMYGNB-GYKMGIIDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2048335
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 70 73 0 0 0 0 0 0 0 0999 V2000 -7.7255 0.1547 1.6789 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4717 0.1067 0.7694 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6213 -0.8057 -0.3606 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5012 0.8863 1.1345 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1857 1.1043 0.5349 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8589 0.2294 -0.5929 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4625 0.5507 -1.1963 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3762 1.9375 -1.6878 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4535 0.0463 -0.2633 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6334 -1.4514 -0.1071 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2449 -2.0318 -0.2703 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5991 -0.9070 0.1878 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0552 -1.0531 0.0207 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5250 -2.1065 1.0149 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9911 -2.3313 0.7086 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7219 -1.0133 0.7894 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8234 -0.9777 1.5339 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5385 0.2845 1.6251 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7602 0.3105 1.7838 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6784 1.5049 1.5119 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9555 1.3807 0.2079 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1660 0.1336 0.0422 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2015 -0.2424 -1.4508 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7158 0.2483 0.4690 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0632 1.4562 -0.0882 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5785 1.4883 0.0325 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0109 0.2598 -0.6019 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3252 0.2257 -2.0398 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6808 1.0375 2.3331 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8021 -0.7961 2.2355 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5732 0.2709 0.9870 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8652 -1.5937 -0.4778 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5871 -1.4233 -0.2376 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8432 -0.2598 -1.3113 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7422 1.4813 2.0734 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9926 2.1977 0.3275 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4517 0.9306 1.4008 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7808 -0.8239 -0.1779 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5993 0.1876 -1.3970 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4495 -0.1195 -2.1107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4124 2.2434 -2.0250 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7566 2.0652 -2.6018 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1170 2.6891 -0.9086 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5997 0.5395 0.7447 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2461 -1.9039 -0.9116 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0293 -1.7241 0.8965 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1168 -2.9660 0.3148 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0768 -2.2127 -1.3606 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3726 -0.6989 1.2513 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3954 -1.3917 -0.9600 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9929 -3.0575 0.8930 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4702 -1.7136 2.0634 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0528 -2.7849 -0.2943 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4475 -3.0690 1.3993 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1665 -1.8671 2.0484 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9802 1.5059 2.3626 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3096 2.4222 1.4889 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3758 2.3039 0.0084 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7568 1.3863 -0.5918 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3239 -1.3213 -1.6137 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1301 0.2198 -1.8969 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3198 0.1021 -1.9873 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7024 0.2791 1.5763 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4123 1.7052 -1.1132 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4275 2.3287 0.5382 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3132 1.4518 1.1145 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2199 2.4284 -0.4369 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5236 0.0169 -2.7237 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0554 -0.6066 -2.2724 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8680 1.1522 -2.3157 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 2 3 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 7 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 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 6 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 6 27 9 1 0 27 12 1 0 24 13 1 0 22 16 1 0 1 29 1 0 1 30 1 0 1 31 1 0 3 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 6 38 1 0 6 39 1 0 7 40 1 6 8 41 1 0 8 42 1 0 8 43 1 0 9 44 1 1 10 45 1 0 10 46 1 0 11 47 1 0 11 48 1 0 12 49 1 1 13 50 1 6 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 17 55 1 0 20 56 1 0 20 57 1 0 21 58 1 0 21 59 1 0 23 60 1 0 23 61 1 0 23 62 1 0 24 63 1 1 25 64 1 0 25 65 1 0 26 66 1 0 26 67 1 0 28 68 1 0 28 69 1 0 28 70 1 0 M END

Standard InCHIKey	ROLSKNVQSMYGNB-GYKMGIIDSA-N
Standard InCHI	InChI=1S/C27H42O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h7,17,19,22-25H,6,8-16H2,1-5H3/t19-,22+,23-,24+,25+,26+,27-/m1/s1
SMILES	CC(C)=CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	382.32	Volume:	442.203 ? Van der Waals volume.
Dense:	0.865	LogP:	7.179 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.789 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-7.207 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	22.0
TPSA:	17.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.46	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.186	Fsp³:	0.815
MCE-18:	66.857 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.743	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.749	Promiscuous compounds:	0.366

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.667	MDCK Permeability:	-4.93
Pgp-inhibitor:	0.467	Pgp-substrate:	0.001
PAMPA:	0.001 ? 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):	0.0
20% Bioavailability (F20%):	0.017	30% Bioavailability (F30%):	0.176
50% Bioavailability (F50%):	0.849

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.165	MRP1:	0.029
Plasma Protein Binding (PPB):	96.941%	Volume Distribution (VD):	-0.074
Fu:	3.193% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.552
BSEP inhibitor:	0.761

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.978
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.175
CYP2D6-inhibitor:	0.12	CYP2D6-substrate:	0.652
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.975 ? 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):

13.306

Half-life (T1/2):

0.318

ADMET: Toxicity

hERG Blockers:	0.23	hERG Blockers (10um):	0.601
Human Hepatotoxicity (H-HT):	0.702	Drug-induced Liver Injury (DILI):	0.306
AMES Toxicity:	0.139	Rat Oral Acute Toxicity:	0.148
Maximum Recommended Daily Dose:	0.317	Skin Sensitization:	0.958
Carcinogencity:	0.825	Eye Corrosion:	0.723
Eye Irritation:	0.977	Respiratory Toxicity:	0.803
Drug-induced Neurotoxicity:	0.392	Ototoxicity:	0.32
Hematotoxicity:	0.555	Drug-induced Nephrotoxicity:	0.446
Genotoxicity:	0.092	RPMI-8226 Immunitoxicity:	0.05
A549 Cytotoxicity:	0.172	Hek293 Cytotoxicity:	0.386
BCF:	2.963 ? 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:	5.032 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.728 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.944 ? 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
NPO57783	Onchidiopsis variegata	Genus	Velutinidae	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
Activity	3

Activity Type	# Activity
Individual protein	1
Unchecked	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1793	Individual protein	Putative cytochrome P450 125	Mycobacterium tuberculosis	Activity	n.a.	n.a.	n.a.	PMID[22647881]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT28438	Unchecked	Unchecked	n.a.	Activity	n.a.	n.a.	n.a.	PMID[22647881]

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 NPC602429 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	20585
0.1-0.2	25097
0.2-0.3	3836
0.3-0.4	261
0.4-0.5	41
0.5-0.6	22
0.6-0.7	7
0.7-0.8	1
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
0.8125	Intermediate Similarity	NPC282593
0.7959	Intermediate Similarity	NPC35734
0.7959	Intermediate Similarity	NPC159577
0.78	Intermediate Similarity	NPC149203
0.7143	Intermediate Similarity	NPC307176
0.7143	Intermediate Similarity	NPC321874
0.6964	Remote Similarity	NPC320514
0.6923	Remote Similarity	NPC115023
0.6731	Remote Similarity	NPC214043
0.6731	Remote Similarity	NPC85774
0.6667	Remote Similarity	NPC249312
0.6481	Remote Similarity	NPC237712
0.6071	Remote Similarity	NPC303613
0.5962	Remote Similarity	NPC139397
0.5862	Remote Similarity	NPC469948
0.5741	Remote Similarity	NPC2634
0.5741	Remote Similarity	NPC265782
0.5741	Remote Similarity	NPC251929
0.5667	Remote Similarity	NPC309603
0.5536	Remote Similarity	NPC255021
0.5536	Remote Similarity	NPC227064
0.5536	Remote Similarity	NPC474228
0.5536	Remote Similarity	NPC329043
0.5536	Remote Similarity	NPC58841
0.5536	Remote Similarity	NPC161423
0.5517	Remote Similarity	NPC323765
0.5484	Remote Similarity	NPC190211
0.5439	Remote Similarity	NPC144258
0.5439	Remote Similarity	NPC327115
0.5167	Remote Similarity	NPC310010
0.5167	Remote Similarity	NPC326627
0.5152	Remote Similarity	NPC187159
0.5085	Remote Similarity	NPC328539
0.5082	Remote Similarity	NPC473999
0.5079	Remote Similarity	NPC489872

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC602429 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6744
0.1-0.2	2122
0.2-0.3	200
0.3-0.4	57
0.4-0.5	9
0.5-0.6	10
0.6-0.7	1
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
0.7143	Intermediate Similarity	NPD4747	Phase 4
0.614	Remote Similarity	NPD5737	Phase 4
0.5965	Remote Similarity	NPD6938	Clinical (unspecified phase)
0.5965	Remote Similarity	NPD6939	Phase 3
0.5932	Remote Similarity	NPD6672	Phase 4
0.5741	Remote Similarity	NPD4691	Approved
0.5536	Remote Similarity	NPD3666	Phase 4
0.5536	Remote Similarity	NPD4221	Phase 4
0.55	Remote Similarity	NPD6409	Approved
0.5424	Remote Similarity	NPD5330	Phase 4
0.5254	Remote Similarity	NPD4693	Phase 3
0.5167	Remote Similarity	NPD4753	Phase 2

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