NPASS Compound

Natural Product: NPC219232

Natural Product ID	NPC219232
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Mooloolabene B
IUPAC Name	(1S,4aR,6aS,10aS,10bR,12aS)-7,7,10a,12a-tetramethyl-4,4a,6,6a,8,9,10,10b,11,12-decahydro-1H-chrysene-1,2-dicarbaldehyde
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL472502
PubChem CID	11994180
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 60 63 0 0 0 0 0 0 0 0999 V2000 -4.2259 1.8106 0.9562 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7540 0.4089 0.6285 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5243 -0.5222 1.5740 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1850 0.0867 -0.7581 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5501 -1.1007 -1.3847 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3080 -1.5936 -0.7330 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5266 -0.4099 -0.2219 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2035 0.5010 -1.3799 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2271 -0.8151 0.4254 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5484 -1.8233 -0.3626 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9083 -1.9649 0.3391 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6578 -0.6969 0.0248 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7888 -0.6504 -1.5041 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0027 0.5314 0.5724 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5228 1.7086 -0.1947 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9982 1.6078 -0.2562 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7178 0.5629 0.0576 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1668 0.6469 -0.0660 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9219 -0.3256 0.2205 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0840 -0.7231 0.5425 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2030 -0.8923 1.9872 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8020 -1.8589 2.4410 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5314 0.4511 0.6546 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1429 1.5427 0.9456 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6070 1.6430 1.0712 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2973 0.3252 0.8653 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.3466 1.7337 1.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8598 2.0799 1.9684 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9935 2.5445 0.1819 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4481 -1.5773 1.2315 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6041 -0.2519 1.5531 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1017 -0.4842 2.5991 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1390 1.0016 -1.4144 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2945 -0.1286 -0.7064 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3498 -0.8380 -2.4656 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2547 -1.9807 -1.4599 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4884 -2.3531 0.0448 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6794 -2.0820 -1.5088 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3778 -0.0157 -2.3689 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1383 0.8109 -1.4062 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7854 1.4455 -1.3667 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5139 -1.2832 1.4106 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6838 -1.4886 -1.4107 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0015 -2.7674 -0.3596 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4860 -2.8090 -0.0718 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7031 -2.0635 1.4248 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7971 -0.3177 -1.8201 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0226 -0.0414 -1.9781 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6791 -1.6864 -1.9362 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3509 0.6857 1.6365 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0886 1.8384 -1.1892 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2963 2.6632 0.3648 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5060 2.5081 -0.6002 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6059 1.5606 -0.4101 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5678 -1.5931 0.0383 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7977 -0.2202 2.7365 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4130 2.4818 1.1163 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9662 2.4460 0.4013 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8269 1.9984 2.1192 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1309 -0.2660 1.8132 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 6 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 6 12 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 17 20 1 0 20 21 1 0 21 22 2 0 14 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 2 1 0 26 7 1 0 23 9 1 0 20 12 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 0 3 31 1 0 3 32 1 0 4 33 1 0 4 34 1 0 5 35 1 0 5 36 1 0 6 37 1 0 6 38 1 0 8 39 1 0 8 40 1 0 8 41 1 0 9 42 1 1 10 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 13 47 1 0 13 48 1 0 13 49 1 0 14 50 1 1 15 51 1 0 15 52 1 0 16 53 1 0 18 54 1 0 20 55 1 6 21 56 1 0 24 57 1 0 25 58 1 0 25 59 1 0 26 60 1 1 M END

Standard InCHIKey	ZUQQZYOCHBYEJX-AIGJZXDYSA-N
Standard InCHI	InChI=1S/C24H34O2/c1-22(2)11-5-12-24(4)19-10-13-23(3)18(17(19)7-9-21(22)24)8-6-16(14-25)20(23)15-26/h6-7,14-15,18-21H,5,8-13H2,1-4H3/t18-,19-,20+,21-,23-,24+/m0/s1
SMILES	CC1(C)CCC[C@]2(C)[C@H]3CC[C@@]4(C)[C@@H](CC=C(C=O)[C@H]4C=O)C3=CC[C@@H]12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.26	Volume:	396.469 ? Van der Waals volume.
Dense:	0.894	LogP:	5.111 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.942 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.559 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	23.0
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:	0.483	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.726	Fsp³:	0.75
MCE-18:	72.0 ? 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:	0.674	Fluc inhibitor:	0.328 ? 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:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.772	Promiscuous compounds:	0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.509	MDCK Permeability:	-4.644
Pgp-inhibitor:	0.847	Pgp-substrate:	0.0
PAMPA:	0.04 ? 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):	0.003
20% Bioavailability (F20%):	0.04	30% Bioavailability (F30%):	0.2
50% Bioavailability (F50%):	0.768

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.822	MRP1:	0.033
Plasma Protein Binding (PPB):	97.617%	Volume Distribution (VD):	0.388
Fu:	2.735% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.389
BSEP inhibitor:	0.955

ADMET: Metabolism

CYP1A2-inhibitor:	0.079	CYP1A2-substrate:	0.961
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.353
CYP2C9-inhibitor:	0.062	CYP2C9-substrate:	0.225
CYP2D6-inhibitor:	0.961	CYP2D6-substrate:	0.734
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.665
HLM stability:	0.995 ? 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):

7.547

Half-life (T1/2):

0.615

ADMET: Toxicity

hERG Blockers:	0.044	hERG Blockers (10um):	0.246
Human Hepatotoxicity (H-HT):	0.514	Drug-induced Liver Injury (DILI):	0.385
AMES Toxicity:	0.396	Rat Oral Acute Toxicity:	0.325
Maximum Recommended Daily Dose:	0.775	Skin Sensitization:	0.909
Carcinogencity:	0.953	Eye Corrosion:	0.465
Eye Irritation:	0.939	Respiratory Toxicity:	0.771
Drug-induced Neurotoxicity:	0.412	Ototoxicity:	0.194
Hematotoxicity:	0.516	Drug-induced Nephrotoxicity:	0.697
Genotoxicity:	0.949	RPMI-8226 Immunitoxicity:	0.051
A549 Cytotoxicity:	0.167	Hek293 Cytotoxicity:	0.672
BCF:	2.627 ? 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:	5.791 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.568 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	7.41 ? 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
NPO20034	Hyattella intestinalis	Species	Spongiidae	Eukaryota	n.a.	Inner Gneerings, a group of shoals off Mooloolaba (Australia)	2005-JUL	PMID[17125226]
NPO21592	Urtica circularis	Species	Urticaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21608987]
NPO19293	Tabebuia cassinoides	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7153777]
NPO18198	Selaginella willdenowii	Species	Selaginellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19595	Lathyrus chloranthus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21265	Teucrium webbianum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20034	Hyattella intestinalis	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19439	Calea zacatechichi	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12814	Daphne retusa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12814	Daphne retusa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20034	Hyattella intestinalis	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21265	Teucrium webbianum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19439	Calea zacatechichi	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21592	Urtica circularis	Species	Urticaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18198	Selaginella willdenowii	Species	Selaginellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17690	Sideritis sventenii	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19735	Euonymus pellucidifolius	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19293	Tabebuia cassinoides	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12814	Daphne retusa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16397	Didymocarpus oblonga	Species	Gesneriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19595	Lathyrus chloranthus	Species	Fabaceae	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
IC50	1

Activity Type	# Activity
Cell line	1

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
NPT168	Cell line	P388	Mus musculus	IC50	=	1.2	ug.mL-1	PMID[17125226]

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 NPC219232 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	26375
0.1-0.2	20857
0.2-0.3	2393
0.3-0.4	199
0.4-0.5	22
0.5-0.6	4
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC128346
0.7037	Intermediate Similarity	NPC2709
0.6977	Remote Similarity	NPC4370
0.6977	Remote Similarity	NPC290350
0.6977	Remote Similarity	NPC481947
0.6458	Remote Similarity	NPC211641
0.5849	Remote Similarity	NPC115515
0.55	Remote Similarity	NPC118266
0.5455	Remote Similarity	NPC307258
0.5263	Remote Similarity	NPC606859

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC219232 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7397
0.1-0.2	1730
0.2-0.3	22
0.3-0.4	1
0.4-0.5	0
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