NPASS Compound

Structure

NPC259989 OpenBabel07101719252D 27 31 0 0 1 0 0 0 0 0999 V2000 -5.4934 4.5025 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7463 1.8262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6355 5.0164 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2959 2.7191 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2372 3.7060 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2767 3.4278 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9026 -0.3884 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4773 3.5027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1983 0.9898 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7616 4.5304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2975 2.7754 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2170 3.5059 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4445 2.7350 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7687 0.1116 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9035 -0.4287 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3797 2.0420 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4899 0.3419 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6033 3.0167 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1999 1.0461 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7455 3.5306 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7495 1.9389 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9916 2.8735 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7612 1.7865 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3836 1.9535 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6007 0.7994 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3031 0.9568 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 1 3 1 0 0 0 0 1 8 1 0 0 0 0 2 4 1 0 0 0 0 2 9 1 0 0 0 0 3 10 1 0 0 0 0 4 11 1 0 0 0 0 5 6 1 0 0 0 0 5 12 2 0 0 0 0 6 13 2 0 0 0 0 7 14 1 0 0 0 0 7 15 1 0 0 0 0 14 26 1 0 0 0 0 15 27 1 0 0 0 0 16 18 1 0 0 0 0 17 19 1 0 0 0 0 18 8 1 6 0 0 0 18 20 1 0 0 0 0 19 9 1 1 0 0 0 19 21 1 0 0 0 0 20 10 1 1 0 0 0 20 22 1 0 0 0 0 21 11 1 6 0 0 0 21 23 1 0 0 0 0 22 12 1 6 0 0 0 22 24 1 0 0 0 0 23 13 1 1 0 0 0 23 25 1 0 0 0 0 24 16 1 1 0 0 0 24 26 1 0 0 0 0 25 17 1 1 0 0 0 25 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	368.32
Volume:	414.894
LogP:	4.599
LogD:	4.967
LogS:	-3.644
# Rotatable Bonds:	0
TPSA:	24.06
# H-Bond Aceptor:	2
# H-Bond Donor:	2
# Rings:	5
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.624
Synthetic Accessibility Score:	5.19
Fsp3:	0.84
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.316
MDCK Permeability:	1.3165582458896097e-05
Pgp-inhibitor:	0.041
Pgp-substrate:	0.992
Human Intestinal Absorption (HIA):	0.046
20% Bioavailability (F20%):	0.884
30% Bioavailability (F30%):	0.932

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.063
Plasma Protein Binding (PPB):	62.32377624511719%
Volume Distribution (VD):	0.859
Pgp-substrate:	18.086109161376953%

ADMET: Metabolism

CYP1A2-inhibitor:	0.127
CYP1A2-substrate:	0.763
CYP2C19-inhibitor:	0.19
CYP2C19-substrate:	0.895
CYP2C9-inhibitor:	0.048
CYP2C9-substrate:	0.335
CYP2D6-inhibitor:	0.899
CYP2D6-substrate:	0.925
CYP3A4-inhibitor:	0.943
CYP3A4-substrate:	0.549

ADMET: Excretion

Clearance (CL):	3.66
Half-life (T1/2):	0.121

ADMET: Toxicity

hERG Blockers:	0.929
Human Hepatotoxicity (H-HT):	0.568
Drug-inuced Liver Injury (DILI):	0.876
AMES Toxicity:	0.23
Rat Oral Acute Toxicity:	0.56
Maximum Recommended Daily Dose:	0.427
Skin Sensitization:	0.965
Carcinogencity:	0.021
Eye Corrosion:	0.145
Eye Irritation:	0.012
Respiratory Toxicity:	0.876

Download Data

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

Natural Product: NPC259989

Natural Product ID:	NPC259989
*Common Name:**	Haliclonadiamine
IUPAC Name:	n.a.
Synonyms:	Haliclonadiamine
Standard InCHIKey:	ZKTFUNZCYRUILZ-ROZCUQDQSA-N
Standard InCHI:	InChI=1S/C25H40N2/c1-3-10-20-18(8-1)16-24-22(20)12-5-6-13-23-21-11-4-2-9-19(21)17-25(23)27-15-7-14-26-24/h5-6,12-13,18-27H,1-4,7-11,14-17H2/b12-5+,13-6+/t18-,19-,20+,21+,22-,23-,24-,25+/m0/s1
SMILES:	C1CC[C@@H]2[C@@H](C1)C[C@H]1[C@H]2/C=C/C=C/[C@H]2[C@@H]3CCCC[C@H]3C[C@H]2NCCCN1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2177349
PubChem CID:	10316977
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004707] Organic nitrogen compounds [CHEMONTID:0000278] Organonitrogen compounds [CHEMONTID:0002449] Amines [CHEMONTID:0002451] Secondary amines [CHEMONTID:0002228] Dialkylamines

*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
NPO20721	Halichondria panicea	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20695474]
NPO33415	neopetrosia cf exigua	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[25585025]
NPO20721	Halichondria panicea	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	PMID[27035556]
NPO20721	Halichondria panicea	Species	Halichondriidae	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	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
EC50	1
GI50	3
IC50	4
Others	3

Activity Type	# Activity
Cell Line	6
Individual Protein	1
NON-MOLECULAR	2
Organism	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT401	Cell Line	786-0	Homo sapiens	IC50	=	15100.0	nM	PMID[503924]
NPT401	Cell Line	786-0	Homo sapiens	Inhibition	=	20.0	%	PMID[503924]
NPT3973	Individual Protein	Endothelial PAS domain-containing protein 1	Homo sapiens	EC50	=	14800.0	nM	PMID[503924]
NPT376	Cell Line	A498	Homo sapiens	GI50	=	5900.0	nM	PMID[503925]
NPT371	Cell Line	UO-31	Homo sapiens	GI50	=	8000.0	nM	PMID[503925]
NPT399	Cell Line	SF-295	Homo sapiens	GI50	=	6300.0	nM	PMID[503925]
NPT1229	Cell Line	Huh-7	Homo sapiens	IC50	=	3600.0	nM	PMID[503926]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	16100.0	nM	PMID[503924]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	15500.0	nM	PMID[503924]
NPT2	Others	Unspecified		Inhibition	=	50.0	%	PMID[503924]
NPT602	Organism	Mycobacterium smegmatis	Mycobacterium smegmatis	IZ	=	16.0	mm	PMID[503926]

☑ 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 NPC259989 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	362
0.1-0.2	7930
0.2-0.3	21861
0.3-0.4	11138
0.4-0.5	1225
0.5-0.6	135
0.6-0.7	29
0.7-0.8	7
0.8-0.85	4
0.85-0.9	0
0.9-0.95	2
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC174803
0.8028	Intermediate Similarity	NPC472544
0.7683	Intermediate Similarity	NPC329782
0.7683	Intermediate Similarity	NPC152039
0.7683	Intermediate Similarity	NPC118329
0.759	Intermediate Similarity	NPC472312
0.7561	Intermediate Similarity	NPC12035
0.747	Intermediate Similarity	NPC474122
0.7229	Intermediate Similarity	NPC211322
0.7126	Intermediate Similarity	NPC24733
0.7073	Intermediate Similarity	NPC7214
0.7011	Intermediate Similarity	NPC471867
0.7	Intermediate Similarity	NPC21773
0.6951	Remote Similarity	NPC125828
0.6897	Remote Similarity	NPC171639
0.6829	Remote Similarity	NPC476904
0.679	Remote Similarity	NPC265789
0.6782	Remote Similarity	NPC283277
0.6566	Remote Similarity	NPC58200
0.6538	Remote Similarity	NPC476559
0.6533	Remote Similarity	NPC231129
0.6447	Remote Similarity	NPC82919
0.6437	Remote Similarity	NPC57599
0.6404	Remote Similarity	NPC215474
0.6265	Remote Similarity	NPC472543
0.625	Remote Similarity	NPC469970
0.6237	Remote Similarity	NPC43308
0.6211	Remote Similarity	NPC84171
0.62	Remote Similarity	NPC135799
0.6162	Remote Similarity	NPC167419
0.6162	Remote Similarity	NPC474164
0.6154	Remote Similarity	NPC21667
0.6139	Remote Similarity	NPC118275
0.6125	Remote Similarity	NPC53276
0.6104	Remote Similarity	NPC472830
0.6095	Remote Similarity	NPC159367
0.6024	Remote Similarity	NPC271640
0.6022	Remote Similarity	NPC147513
0.602	Remote Similarity	NPC476754
0.6	Remote Similarity	NPC474086
0.5957	Remote Similarity	NPC157479
0.5922	Remote Similarity	NPC176012
0.5918	Remote Similarity	NPC476752
0.5918	Remote Similarity	NPC476753
0.5875	Remote Similarity	NPC219621
0.5851	Remote Similarity	NPC152684
0.5851	Remote Similarity	NPC75810
0.5833	Remote Similarity	NPC472313
0.5825	Remote Similarity	NPC474582
0.58	Remote Similarity	NPC329430
0.5789	Remote Similarity	NPC56107
0.5789	Remote Similarity	NPC166458
0.5784	Remote Similarity	NPC91604
0.578	Remote Similarity	NPC474459
0.578	Remote Similarity	NPC79238
0.5755	Remote Similarity	NPC233256
0.5755	Remote Similarity	NPC230677
0.5755	Remote Similarity	NPC195841
0.573	Remote Similarity	NPC25110
0.5727	Remote Similarity	NPC474452
0.5699	Remote Similarity	NPC471868
0.5696	Remote Similarity	NPC469769
0.5658	Remote Similarity	NPC472828
0.5644	Remote Similarity	NPC272732
0.5644	Remote Similarity	NPC311164
0.5625	Remote Similarity	NPC472827
0.5625	Remote Similarity	NPC21781
0.5607	Remote Similarity	NPC474695
0.5604	Remote Similarity	NPC473446
0.5604	Remote Similarity	NPC473695

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 NPC259989 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	214
0.1-0.2	908
0.2-0.3	4687
0.3-0.4	2826
0.4-0.5	461
0.5-0.6	52
0.6-0.7	2
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
0.7	Intermediate Similarity	NPD5365	Phase 2
0.6737	Remote Similarity	NPD1738	Approved
0.6237	Remote Similarity	NPD4145	Approved
0.6237	Remote Similarity	NPD4146	Approved
0.6164	Remote Similarity	NPD3722	Approved
0.6164	Remote Similarity	NPD3721	Approved
0.6042	Remote Similarity	NPD5915	Approved
0.5979	Remote Similarity	NPD4543	Discontinued
0.5895	Remote Similarity	NPD3426	Approved
0.5895	Remote Similarity	NPD3428	Approved
0.5888	Remote Similarity	NPD8010	Approved
0.5888	Remote Similarity	NPD8009	Approved
0.5859	Remote Similarity	NPD735	Approved
0.5859	Remote Similarity	NPD736	Approved
0.5844	Remote Similarity	NPD628	Phase 3
0.5844	Remote Similarity	NPD625	Approved
0.5844	Remote Similarity	NPD627	Approved
0.5844	Remote Similarity	NPD626	Phase 3
0.58	Remote Similarity	NPD5554	Approved
0.5729	Remote Similarity	NPD2002	Discontinued
0.5699	Remote Similarity	NPD4169	Approved
0.5699	Remote Similarity	NPD4170	Approved
0.5699	Remote Similarity	NPD4701	Clinical (unspecified phase)
0.5686	Remote Similarity	NPD713	Clinical (unspecified phase)
0.5686	Remote Similarity	NPD528	Clinical (unspecified phase)

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