NPASS Compound

Natural Product: NPC527452

Natural Product ID	NPC527452
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(8~{S},9~{S},10~{R},13~{S},14~{S},17~{R})-10,13-dimethyl-17-[(1~{S})-1-methyl-2-oxo-propyl]-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
IUPAC Name	(8~{S},9~{S},10~{R},13~{S},14~{S},17~{R})-10,13-dimethyl-17-[(1~{S})-1-methyl-2-oxo-propyl]-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
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 59 62 0 0 0 0 0 0 0 0999 V2000 5.7136 1.0924 -0.3591 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0758 0.2386 0.6608 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6822 0.2083 1.7529 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8422 -0.5516 0.5176 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6596 -1.3626 1.7769 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7186 0.2504 0.0982 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9326 0.8923 -1.2469 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5170 1.1923 -1.7868 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6484 0.8274 -0.6464 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7735 0.6080 -0.9407 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4246 1.9487 -1.2058 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7010 2.1780 -0.4790 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5653 1.0124 -0.3146 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8663 1.0797 -0.2915 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6495 -0.1363 -0.1225 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7925 -0.2703 -0.6272 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0628 -1.2418 0.6743 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5953 -1.0990 0.9072 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8981 -0.3285 -0.1650 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9763 -1.0296 -1.4842 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4784 -0.0154 0.2409 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7539 -1.2167 0.7419 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6541 -0.7646 1.1614 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3826 -0.4031 -0.0829 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3588 -1.4511 -1.1404 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8446 1.0170 -0.1989 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5180 2.1683 -0.1501 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5861 0.7823 -1.3943 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0722 -1.3251 -0.2817 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2763 -2.3759 1.6032 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1378 -0.7821 2.5616 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6943 -1.5324 2.1869 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5389 1.1065 0.8067 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4095 0.1475 -1.9535 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4660 1.8342 -1.2459 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2968 0.5131 -2.6499 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4422 2.2491 -2.1128 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7521 1.6029 0.1392 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9552 0.0001 -1.8734 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5822 2.1166 -2.3112 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7321 2.7906 -0.9172 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2556 2.9881 -1.0117 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4855 2.6094 0.5386 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3725 2.0275 -0.3976 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2909 -2.2331 0.1840 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5598 -1.2474 1.6859 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3569 -0.6029 1.8842 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1570 -2.1337 0.9374 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8934 -1.6825 -1.4740 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0746 -0.3518 -2.3516 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0974 -1.6868 -1.6905 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5299 0.7276 1.0557 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2270 -1.5883 1.6672 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7308 -2.0307 0.0190 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0381 -1.5870 1.7522 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4985 0.1469 1.7710 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3477 -1.5688 -1.6643 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6239 -1.2814 -1.9534 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1098 -2.4757 -0.7364 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 1 0 4 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 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 6 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 6 24 6 1 0 24 9 1 0 21 10 1 0 19 13 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 6 5 30 1 0 5 31 1 0 5 32 1 0 6 33 1 1 7 34 1 0 7 35 1 0 8 36 1 0 8 37 1 0 9 38 1 1 10 39 1 6 11 40 1 0 11 41 1 0 12 42 1 0 12 43 1 0 14 44 1 0 17 45 1 0 17 46 1 0 18 47 1 0 18 48 1 0 20 49 1 0 20 50 1 0 20 51 1 0 21 52 1 1 22 53 1 0 22 54 1 0 23 55 1 0 23 56 1 0 25 57 1 0 25 58 1 0 25 59 1 0 M END

Standard InCHIKey	MUQIYHIBKQKOOI-KZJFZMNRSA-N
Standard InCHI	InChI=1S/C23H34O2/c1-14(15(2)24)19-7-8-20-18-6-5-16-13-17(25)9-11-22(16,3)21(18)10-12-23(19,20)4/h13-14,18-21H,5-12H2,1-4H3/t14-,18+,19-,20+,21+,22+,23-/m1/s1
SMILES	CC(=O)[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:	342.26	Volume:	381.809 ? Van der Waals volume.
Dense:	0.896	LogP:	3.64 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.318 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.0 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	22.0
TPSA:	34.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.677	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.195	Fsp³:	0.826
MCE-18:	69.333 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.398	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.021 ? 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:	0.636	Promiscuous compounds:	0.896

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.688	MDCK Permeability:	-4.842
Pgp-inhibitor:	0.807	Pgp-substrate:	0.001
PAMPA:	0.002 ? 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%):	0.019	30% Bioavailability (F30%):	0.072
50% Bioavailability (F50%):	0.542

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.244	MRP1:	0.185
Plasma Protein Binding (PPB):	96.738%	Volume Distribution (VD):	0.112
Fu:	3.835% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.612
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.978
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.008
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.487
CYP2D6-inhibitor:	0.208	CYP2D6-substrate:	0.201
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.836 ? 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):

14.114

Half-life (T1/2):

0.543

ADMET: Toxicity

hERG Blockers:	0.204	hERG Blockers (10um):	0.41
Human Hepatotoxicity (H-HT):	0.716	Drug-induced Liver Injury (DILI):	0.494
AMES Toxicity:	0.227	Rat Oral Acute Toxicity:	0.09
Maximum Recommended Daily Dose:	0.59	Skin Sensitization:	0.868
Carcinogencity:	0.94	Eye Corrosion:	0.261
Eye Irritation:	0.973	Respiratory Toxicity:	0.792
Drug-induced Neurotoxicity:	0.191	Ototoxicity:	0.41
Hematotoxicity:	0.838	Drug-induced Nephrotoxicity:	0.552
Genotoxicity:	0.665	RPMI-8226 Immunitoxicity:	0.034
A549 Cytotoxicity:	0.059	Hek293 Cytotoxicity:	0.588
BCF:	1.003 ? 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:	3.604 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.102 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.541 ? 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
NPO21744	Aldisa smaragdina	Species	Dorididae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21744	Aldisa smaragdina	Species	Dorididae	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

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 NPC527452 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	20574
0.1-0.2	25616
0.2-0.3	3420
0.3-0.4	171
0.4-0.5	38
0.5-0.6	21
0.6-0.7	5
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8182	Intermediate Similarity	NPC307176
0.8182	Intermediate Similarity	NPC321874
0.7917	Intermediate Similarity	NPC249312
0.7872	Intermediate Similarity	NPC35734
0.766	Intermediate Similarity	NPC282593
0.75	Intermediate Similarity	NPC159577
0.75	Intermediate Similarity	NPC115023
0.75	Intermediate Similarity	NPC602429
0.7347	Intermediate Similarity	NPC149203
0.7292	Intermediate Similarity	NPC214043
0.7292	Intermediate Similarity	NPC85774
0.7	Intermediate Similarity	NPC237712
0.6545	Remote Similarity	NPC320514
0.6458	Remote Similarity	NPC139397
0.62	Remote Similarity	NPC2634
0.62	Remote Similarity	NPC265782
0.62	Remote Similarity	NPC251929
0.5962	Remote Similarity	NPC227064
0.5962	Remote Similarity	NPC329043
0.5962	Remote Similarity	NPC58841
0.5962	Remote Similarity	NPC161423
0.5926	Remote Similarity	NPC323765
0.5849	Remote Similarity	NPC144258
0.5849	Remote Similarity	NPC327115
0.5741	Remote Similarity	NPC328539
0.5714	Remote Similarity	NPC469948
0.5636	Remote Similarity	NPC303613
0.5536	Remote Similarity	NPC310010
0.5536	Remote Similarity	NPC326627
0.5484	Remote Similarity	NPC187159
0.5333	Remote Similarity	NPC305039
0.5333	Remote Similarity	NPC205860
0.5254	Remote Similarity	NPC309603
0.5172	Remote Similarity	NPC185936
0.5172	Remote Similarity	NPC168027
0.5094	Remote Similarity	NPC92327
0.5091	Remote Similarity	NPC255021
0.5091	Remote Similarity	NPC474228

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC527452 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6487
0.1-0.2	2391
0.2-0.3	174
0.3-0.4	58
0.4-0.5	20
0.5-0.6	16
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	Drug ID	Developmental Stage
0.8182	Intermediate Similarity	NPD4747	Phase 4
0.6604	Remote Similarity	NPD5737	Phase 4
0.6364	Remote Similarity	NPD6672	Phase 4
0.62	Remote Similarity	NPD4691	Approved
0.5962	Remote Similarity	NPD3666	Phase 4
0.5962	Remote Similarity	NPD4221	Phase 4
0.5893	Remote Similarity	NPD6409	Approved
0.5818	Remote Similarity	NPD5330	Phase 4
0.5818	Remote Similarity	NPD6938	Clinical (unspecified phase)
0.5818	Remote Similarity	NPD6939	Phase 3
0.5636	Remote Similarity	NPD4693	Phase 3
0.5536	Remote Similarity	NPD4753	Phase 2
0.5333	Remote Similarity	NPD6083	Phase 4
0.5333	Remote Similarity	NPD6084	Phase 2
0.5333	Remote Similarity	NPD6684	Phase 4
0.5333	Remote Similarity	NPD6904	Phase 4
0.5333	Remote Similarity	NPD7334	Approved
0.5333	Remote Similarity	NPD7521	Phase 4
0.5246	Remote Similarity	NPD6903	Phase 4
0.5079	Remote Similarity	NPD7513	Clinical (unspecified phase)

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