NPASS Compound

Structure

NPC6902 OpenBabel07101718322D 30 30 0 0 1 0 0 0 0 0999 V2000 -9.0241 2.9004 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2247 -1.2247 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5517 -1.6730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3320 2.6248 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2588 -0.9659 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0582 3.1592 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3510 2.4521 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3851 2.7109 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6780 2.0038 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7121 2.2626 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 3.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3660 2.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0050 1.5555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 3.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2588 -0.9659 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3660 2.3660 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3660 1.3660 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0391 1.8143 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8660 3.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 3.7321 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3660 1.3660 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3320 1.1072 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.7802 2.7802 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5731 3.9392 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5731 -0.2071 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5731 -0.2071 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 2 15 1 0 0 0 0 3 15 1 0 0 0 0 5 26 1 0 0 0 0 6 7 2 0 0 0 0 7 8 1 0 0 0 0 8 9 2 0 0 0 0 9 10 1 0 0 0 0 10 13 2 0 0 0 0 11 12 1 0 0 0 0 11 14 1 0 0 0 0 12 17 1 0 0 0 0 13 18 1 0 0 0 0 14 23 1 0 0 0 0 16 4 1 6 0 0 0 16 20 1 0 0 0 0 16 24 1 0 0 0 0 17 22 1 0 0 0 0 17 25 1 1 0 0 0 18 25 2 3 0 0 0 18 27 1 0 0 0 0 19 15 1 6 0 0 0 19 21 1 0 0 0 0 19 26 1 0 0 0 0 20 23 2 3 0 0 0 20 28 1 0 0 0 0 21 24 2 3 0 0 0 21 29 1 0 0 0 0 22 26 1 0 0 0 0 22 30 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	418.26
Volume:	441.204
LogP:	0.684
LogD:	1.775
LogS:	-3.118
# Rotatable Bonds:	7
TPSA:	126.3
# H-Bond Aceptor:	8
# H-Bond Donor:	6
# Rings:	1
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.297
Synthetic Accessibility Score:	4.607
Fsp3:	0.409
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.922
MDCK Permeability:	2.2057383830542676e-06
Pgp-inhibitor:	0.0
Pgp-substrate:	0.012
Human Intestinal Absorption (HIA):	0.016
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.864

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.034
Plasma Protein Binding (PPB):	94.64309692382812%
Volume Distribution (VD):	0.936
Pgp-substrate:	6.606759071350098%

ADMET: Metabolism

CYP1A2-inhibitor:	0.088
CYP1A2-substrate:	0.955
CYP2C19-inhibitor:	0.281
CYP2C19-substrate:	0.058
CYP2C9-inhibitor:	0.189
CYP2C9-substrate:	0.985
CYP2D6-inhibitor:	0.767
CYP2D6-substrate:	0.916
CYP3A4-inhibitor:	0.045
CYP3A4-substrate:	0.117

ADMET: Excretion

Clearance (CL):	4.074
Half-life (T1/2):	0.841

ADMET: Toxicity

hERG Blockers:	0.005
Human Hepatotoxicity (H-HT):	0.339
Drug-inuced Liver Injury (DILI):	0.861
AMES Toxicity:	0.006
Rat Oral Acute Toxicity:	0.06
Maximum Recommended Daily Dose:	0.036
Skin Sensitization:	0.061
Carcinogencity:	0.069
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.736

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC6902

Natural Product ID:	NPC6902
*Common Name:**	(2E,4E,6E)-N-[(3S,6S,9S)-3,7-Dimethyl-2,5,8-Trioxo-6-Propan-2-Yl-1,4,7-Triazacyclododec-9-Yl]Octa-2,4,6-Trienamide
IUPAC Name:	(2E,4E,6E)-N-[(3S,6S,9S)-3,7-dimethyl-2,5,8-trioxo-6-propan-2-yl-1,4,7-triazacyclododec-9-yl]octa-2,4,6-trienamide
Synonyms:
Standard InCHIKey:	IBQPLRWXHSRNAW-VUOPYGPLSA-N
Standard InCHI:	InChI=1S/C22H34N4O4/c1-6-7-8-9-10-13-18(27)25-17-12-11-14-23-20(28)16(4)24-21(29)19(15(2)3)26(5)22(17)30/h6-10,13,15-17,19H,11-12,14H2,1-5H3,(H,23,28)(H,24,29)(H,25,27)/b7-6+,9-8+,13-10+/t16-,17-,19-/m0/s1
SMILES:	C/C=C/C=C/C=C/C(=N[C@H]1CCCN=C(O)[C@@H](N=C([C@@H](N(C1=O)C)C(C)C)O)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1163977
PubChem CID:	46906560
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0004831] Oligopeptides

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33363	aspergillus sclerotiorum pt06-1	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20503985]

☑ 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	NP ID	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	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	30000.0	nM	PMID[540510]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC6902 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	62
0.1-0.2	9240
0.2-0.3	26190
0.3-0.4	5399
0.4-0.5	1348
0.5-0.6	389
0.6-0.7	61
0.7-0.8	3
0.8-0.85	1
0.85-0.9	1
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9737	High Similarity	NPC284456
0.9481	High Similarity	NPC184473
0.8916	High Similarity	NPC155230
0.8315	Intermediate Similarity	NPC469739
0.7333	Intermediate Similarity	NPC473495
0.6854	Remote Similarity	NPC53858
0.6854	Remote Similarity	NPC84128
0.6742	Remote Similarity	NPC23984
0.6706	Remote Similarity	NPC266888
0.6706	Remote Similarity	NPC256312
0.6706	Remote Similarity	NPC209156
0.6706	Remote Similarity	NPC161774
0.6705	Remote Similarity	NPC31756
0.6703	Remote Similarity	NPC472351
0.6667	Remote Similarity	NPC214532
0.6667	Remote Similarity	NPC196007
0.6667	Remote Similarity	NPC76297
0.6629	Remote Similarity	NPC476117
0.6629	Remote Similarity	NPC476243
0.6629	Remote Similarity	NPC476137
0.6629	Remote Similarity	NPC476156
0.66	Remote Similarity	NPC475758
0.6598	Remote Similarity	NPC38172
0.6593	Remote Similarity	NPC235078
0.6569	Remote Similarity	NPC475149
0.6569	Remote Similarity	NPC471097
0.6556	Remote Similarity	NPC476302
0.6535	Remote Similarity	NPC475791
0.6535	Remote Similarity	NPC13175
0.6505	Remote Similarity	NPC476877
0.6449	Remote Similarity	NPC251122
0.6415	Remote Similarity	NPC171734
0.6381	Remote Similarity	NPC476876
0.6333	Remote Similarity	NPC312315
0.6316	Remote Similarity	NPC315188
0.6289	Remote Similarity	NPC474593
0.6289	Remote Similarity	NPC475801
0.6286	Remote Similarity	NPC205176
0.6263	Remote Similarity	NPC301010
0.6262	Remote Similarity	NPC207820
0.6224	Remote Similarity	NPC474576
0.6216	Remote Similarity	NPC472536
0.6216	Remote Similarity	NPC103391
0.6211	Remote Similarity	NPC477539
0.62	Remote Similarity	NPC280066
0.6196	Remote Similarity	NPC470783
0.6195	Remote Similarity	NPC239357
0.6186	Remote Similarity	NPC320057
0.6162	Remote Similarity	NPC471098
0.6162	Remote Similarity	NPC173763
0.6162	Remote Similarity	NPC62263
0.6161	Remote Similarity	NPC296043
0.614	Remote Similarity	NPC470545
0.6118	Remote Similarity	NPC306696
0.6118	Remote Similarity	NPC250953
0.6106	Remote Similarity	NPC329216
0.6091	Remote Similarity	NPC476875
0.6087	Remote Similarity	NPC470546
0.6071	Remote Similarity	NPC128005
0.6071	Remote Similarity	NPC84182
0.6053	Remote Similarity	NPC470544
0.6034	Remote Similarity	NPC160688
0.5983	Remote Similarity	NPC200964
0.5962	Remote Similarity	NPC220234
0.5948	Remote Similarity	NPC470652
0.5934	Remote Similarity	NPC59867
0.5926	Remote Similarity	NPC292299
0.5926	Remote Similarity	NPC34838
0.5922	Remote Similarity	NPC473597
0.5904	Remote Similarity	NPC105297
0.59	Remote Similarity	NPC477538
0.5889	Remote Similarity	NPC327272
0.5882	Remote Similarity	NPC470654
0.5882	Remote Similarity	NPC470650
0.5882	Remote Similarity	NPC470653
0.5854	Remote Similarity	NPC263207
0.5851	Remote Similarity	NPC475542
0.5849	Remote Similarity	NPC188785
0.5847	Remote Similarity	NPC273185
0.5833	Remote Similarity	NPC6975
0.581	Remote Similarity	NPC475440
0.5798	Remote Similarity	NPC50520
0.5794	Remote Similarity	NPC5864
0.5794	Remote Similarity	NPC301148
0.5794	Remote Similarity	NPC124554
0.5789	Remote Similarity	NPC246005
0.5783	Remote Similarity	NPC6795
0.5773	Remote Similarity	NPC475975
0.5769	Remote Similarity	NPC144780
0.5769	Remote Similarity	NPC134504
0.5769	Remote Similarity	NPC47076
0.5765	Remote Similarity	NPC262615
0.5765	Remote Similarity	NPC128559
0.575	Remote Similarity	NPC471992
0.5741	Remote Similarity	NPC198344
0.5739	Remote Similarity	NPC473819
0.5738	Remote Similarity	NPC101719
0.573	Remote Similarity	NPC97614
0.5726	Remote Similarity	NPC473322
0.5714	Remote Similarity	NPC243964
0.57	Remote Similarity	NPC275715
0.5699	Remote Similarity	NPC191774
0.5688	Remote Similarity	NPC323720
0.5688	Remote Similarity	NPC128303
0.5688	Remote Similarity	NPC124549
0.5686	Remote Similarity	NPC315237
0.5667	Remote Similarity	NPC71684
0.5667	Remote Similarity	NPC202521
0.5656	Remote Similarity	NPC222466
0.5639	Remote Similarity	NPC316008
0.5639	Remote Similarity	NPC313867
0.5636	Remote Similarity	NPC241394
0.5635	Remote Similarity	NPC130309
0.5632	Remote Similarity	NPC187315
0.5612	Remote Similarity	NPC470943
0.561	Remote Similarity	NPC470651
0.561	Remote Similarity	NPC470655
0.5604	Remote Similarity	NPC126186
0.56	Remote Similarity	NPC324506

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC6902 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	67
0.1-0.2	660
0.2-0.3	5341
0.3-0.4	2580
0.4-0.5	431
0.5-0.6	63
0.6-0.7	8
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
0.7126	Intermediate Similarity	NPD7762	Phase 2
0.7126	Intermediate Similarity	NPD7763	Phase 2
0.6667	Remote Similarity	NPD2683	Discontinued
0.6559	Remote Similarity	NPD7760	Phase 2
0.6559	Remote Similarity	NPD7759	Phase 2
0.6235	Remote Similarity	NPD620	Approved
0.6211	Remote Similarity	NPD3723	Clinical (unspecified phase)
0.6023	Remote Similarity	NPD265	Phase 3
0.6023	Remote Similarity	NPD266	Phase 3
0.598	Remote Similarity	NPD7841	Clinical (unspecified phase)
0.5978	Remote Similarity	NPD4815	Discontinued
0.5957	Remote Similarity	NPD1125	Discovery
0.5949	Remote Similarity	NPD1456	Approved
0.593	Remote Similarity	NPD322	Phase 1
0.5918	Remote Similarity	NPD3177	Phase 3
0.59	Remote Similarity	NPD4261	Phase 1
0.5876	Remote Similarity	NPD5791	Phase 2
0.5865	Remote Similarity	NPD8038	Phase 2
0.5765	Remote Similarity	NPD6437	Approved
0.5765	Remote Similarity	NPD6438	Approved
0.5743	Remote Similarity	NPD5792	Clinical (unspecified phase)
0.5743	Remote Similarity	NPD4780	Clinical (unspecified phase)
0.5727	Remote Similarity	NPD2147	Approved
0.5699	Remote Similarity	NPD4278	Clinical (unspecified phase)
0.5686	Remote Similarity	NPD6699	Clinical (unspecified phase)
0.568	Remote Similarity	NPD7979	Clinical (unspecified phase)
0.5679	Remote Similarity	NPD9425	Approved
0.567	Remote Similarity	NPD3733	Clinical (unspecified phase)
0.566	Remote Similarity	NPD4825	Clinical (unspecified phase)
0.5657	Remote Similarity	NPD3176	Clinical (unspecified phase)
0.5635	Remote Similarity	NPD6919	Clinical (unspecified phase)
0.5614	Remote Similarity	NPD2090	Approved
0.561	Remote Similarity	NPD3125	Approved

Bioactivity similarity: Similar Natural Products in NPASS

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