Structure

Physi-Chem Properties

Molecular Weight:  283.19
Volume:  318.115
LogP:  4.646
LogD:  4.021
LogS:  -5.377
# Rotatable Bonds:  0
TPSA:  29.43
# H-Bond Aceptor:  2
# H-Bond Donor:  0
# Rings:  3
# Heavy Atoms:  2

MedChem Properties

QED Drug-Likeness Score:  0.478
Synthetic Accessibility Score:  4.784
Fsp3:  0.579
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:  -4.979
MDCK Permeability:  2.07E-05
Pgp-inhibitor:  0.613
Pgp-substrate:  0.97
Human Intestinal Absorption (HIA):  0.031
20% Bioavailability (F20%):  0.481
30% Bioavailability (F30%):  0.049

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.487
Plasma Protein Binding (PPB):  92.78%
Volume Distribution (VD):  1.894
Pgp-substrate:  4.29%

ADMET: Metabolism

CYP1A2-inhibitor:  0.032
CYP1A2-substrate:  0.246
CYP2C19-inhibitor:  0.433
CYP2C19-substrate:  0.905
CYP2C9-inhibitor:  0.151
CYP2C9-substrate:  0.058
CYP2D6-inhibitor:  0.06
CYP2D6-substrate:  0.112
CYP3A4-inhibitor:  0.759
CYP3A4-substrate:  0.809

ADMET: Excretion

Clearance (CL):  6.558
Half-life (T1/2):  0.099

ADMET: Toxicity

hERG Blockers:  0.001
Human Hepatotoxicity (H-HT):  0.113
Drug-inuced Liver Injury (DILI):  0.354
AMES Toxicity:  0.012
Rat Oral Acute Toxicity:  0.786
Maximum Recommended Daily Dose:  0.826
Skin Sensitization:  0.73
Carcinogencity:  0.849
Eye Corrosion:  0.006
Eye Irritation:  0.019
Respiratory Toxicity:  0.99

Download Data

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

  Natural Product: NPC477581

Natural Product ID:  NPC477581
Common Name*:   Nigelladine A
IUPAC Name:   (8aS)-2,2,4,8a-tetramethyl-6-propan-2-yl-8,9-dihydroindeno[2,1-b]pyridin-7-one
Synonyms:  
Standard InCHIKey:  ZLLJDNGQDGFFLK-IBGZPJMESA-N
Standard InCHI:  InChI=1S/C19H25NO/c1-11(2)13-7-14-17-12(3)8-18(4,5)20-15(17)9-19(14,6)10-16(13)21/h7-8,11H,9-10H2,1-6H3/t19-/m0/s1
SMILES:  CC1=CC(N=C2C1=C3C=C(C(=O)C[C@@]3(C2)C)C(C)C)(C)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   n.a.
PubChem CID:   86302612
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids

*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
NPO2136 Nigella glandulifera Species Ranunculaceae Eukaryota Seeds n.a. n.a. PMID[24593120]
NPO2136 Nigella glandulifera Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[26227777]
NPO2136 Nigella glandulifera Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2136 Nigella glandulifera Species Ranunculaceae 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

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT178 Individual Protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 9970 nM PMID[24593120]

☑ 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 NPC477581 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.9868 High Similarity NPC477582
0.974 High Similarity NPC477583
0.8434 Intermediate Similarity NPC477584
0.7667 Intermediate Similarity NPC249312
0.6962 Remote Similarity NPC165695
0.6951 Remote Similarity NPC310992
0.6867 Remote Similarity NPC256846
0.686 Remote Similarity NPC473171
0.6854 Remote Similarity NPC250632
0.6837 Remote Similarity NPC247220
0.6835 Remote Similarity NPC97322
0.679 Remote Similarity NPC251118
0.6786 Remote Similarity NPC265782
0.6786 Remote Similarity NPC251929
0.6786 Remote Similarity NPC2634
0.675 Remote Similarity NPC167256
0.6744 Remote Similarity NPC474797
0.6744 Remote Similarity NPC474796
0.6744 Remote Similarity NPC329866
0.6709 Remote Similarity NPC25853
0.6706 Remote Similarity NPC54123
0.6706 Remote Similarity NPC181204
0.6667 Remote Similarity NPC27610
0.6667 Remote Similarity NPC94991
0.6667 Remote Similarity NPC266295
0.6667 Remote Similarity NPC226509
0.6667 Remote Similarity NPC139397
0.6667 Remote Similarity NPC56905
0.6667 Remote Similarity NPC212210
0.6628 Remote Similarity NPC474228
0.6628 Remote Similarity NPC303613
0.6628 Remote Similarity NPC251705
0.6628 Remote Similarity NPC470044
0.6628 Remote Similarity NPC470045
0.6591 Remote Similarity NPC469796
0.6591 Remote Similarity NPC469793
0.6588 Remote Similarity NPC260040
0.6588 Remote Similarity NPC35734
0.6588 Remote Similarity NPC159577
0.6588 Remote Similarity NPC282593
0.6588 Remote Similarity NPC307176
0.6582 Remote Similarity NPC259261
0.6556 Remote Similarity NPC170793
0.6548 Remote Similarity NPC260474
0.6548 Remote Similarity NPC87141
0.6548 Remote Similarity NPC188292
0.6543 Remote Similarity NPC32285
0.6535 Remote Similarity NPC140685
0.6512 Remote Similarity NPC115023
0.6512 Remote Similarity NPC5701
0.6512 Remote Similarity NPC234707
0.6512 Remote Similarity NPC470078
0.6505 Remote Similarity NPC152718
0.65 Remote Similarity NPC127582
0.6489 Remote Similarity NPC76283
0.6477 Remote Similarity NPC293803
0.6463 Remote Similarity NPC475124
0.6463 Remote Similarity NPC4638
0.6463 Remote Similarity NPC285371
0.6456 Remote Similarity NPC30215
0.6429 Remote Similarity NPC475523
0.642 Remote Similarity NPC213152
0.6404 Remote Similarity NPC69408
0.6381 Remote Similarity NPC469958
0.6375 Remote Similarity NPC276764
0.6375 Remote Similarity NPC472304
0.6364 Remote Similarity NPC255021
0.6364 Remote Similarity NPC309852
0.6353 Remote Similarity NPC20610
0.6353 Remote Similarity NPC155198
0.6341 Remote Similarity NPC288253
0.6329 Remote Similarity NPC49575
0.6329 Remote Similarity NPC115385
0.6329 Remote Similarity NPC230823
0.6329 Remote Similarity NPC55004
0.6329 Remote Similarity NPC267626
0.6322 Remote Similarity NPC305501
0.6321 Remote Similarity NPC230677
0.6316 Remote Similarity NPC311769
0.6316 Remote Similarity NPC182106
0.631 Remote Similarity NPC323005
0.6279 Remote Similarity NPC182815
0.6265 Remote Similarity NPC469662
0.6265 Remote Similarity NPC150162
0.6265 Remote Similarity NPC6697
0.6265 Remote Similarity NPC473902
0.6264 Remote Similarity NPC189485
0.625 Remote Similarity NPC476141
0.6234 Remote Similarity NPC268564
0.6234 Remote Similarity NPC474141
0.6234 Remote Similarity NPC37644
0.6234 Remote Similarity NPC296311
0.6234 Remote Similarity NPC45283
0.6222 Remote Similarity NPC110725
0.622 Remote Similarity NPC475795
0.6211 Remote Similarity NPC87552
0.6207 Remote Similarity NPC151045
0.6207 Remote Similarity NPC246722
0.6203 Remote Similarity NPC20603
0.6196 Remote Similarity NPC90965
0.6196 Remote Similarity NPC27817
0.619 Remote Similarity NPC470329
0.619 Remote Similarity NPC469598
0.6173 Remote Similarity NPC96551
0.6173 Remote Similarity NPC143834
0.6173 Remote Similarity NPC285594
0.617 Remote Similarity NPC472867
0.617 Remote Similarity NPC469804
0.617 Remote Similarity NPC469806
0.617 Remote Similarity NPC469799
0.617 Remote Similarity NPC469805
0.6154 Remote Similarity NPC283087
0.6147 Remote Similarity NPC175585
0.6145 Remote Similarity NPC202118
0.6145 Remote Similarity NPC472306
0.6145 Remote Similarity NPC197238
0.6139 Remote Similarity NPC476754
0.6136 Remote Similarity NPC225467
0.6136 Remote Similarity NPC190035
0.6136 Remote Similarity NPC474562
0.6129 Remote Similarity NPC469798
0.6129 Remote Similarity NPC469797
0.6129 Remote Similarity NPC474509
0.6122 Remote Similarity NPC259252
0.6118 Remote Similarity NPC92327
0.6118 Remote Similarity NPC176171
0.6118 Remote Similarity NPC187315
0.6111 Remote Similarity NPC476346
0.6111 Remote Similarity NPC255650
0.6105 Remote Similarity NPC21667
0.6105 Remote Similarity NPC474790
0.6105 Remote Similarity NPC474976
0.6105 Remote Similarity NPC118423
0.6105 Remote Similarity NPC279639
0.6105 Remote Similarity NPC3856
0.6092 Remote Similarity NPC474060
0.6091 Remote Similarity NPC476290
0.6067 Remote Similarity NPC180015
0.6067 Remote Similarity NPC56747
0.6067 Remote Similarity NPC130016
0.6067 Remote Similarity NPC109576
0.6053 Remote Similarity NPC32351
0.6053 Remote Similarity NPC58970
0.6053 Remote Similarity NPC163984
0.6053 Remote Similarity NPC176819
0.6049 Remote Similarity NPC311852
0.6049 Remote Similarity NPC308108
0.6049 Remote Similarity NPC170799
0.6047 Remote Similarity NPC176107
0.6047 Remote Similarity NPC193770
0.6047 Remote Similarity NPC290350
0.6047 Remote Similarity NPC4370
0.6044 Remote Similarity NPC40353
0.6044 Remote Similarity NPC1254
0.6038 Remote Similarity NPC58200
0.6026 Remote Similarity NPC69898
0.6026 Remote Similarity NPC295777
0.6024 Remote Similarity NPC60565
0.6023 Remote Similarity NPC214770
0.6023 Remote Similarity NPC477856
0.6022 Remote Similarity NPC471597
0.602 Remote Similarity NPC472614
0.602 Remote Similarity NPC163016
0.602 Remote Similarity NPC75315
0.6019 Remote Similarity NPC476449
0.6 Remote Similarity NPC473733
0.6 Remote Similarity NPC3511
0.6 Remote Similarity NPC268122
0.6 Remote Similarity NPC472239
0.6 Remote Similarity NPC142253
0.5982 Remote Similarity NPC476269
0.5981 Remote Similarity NPC474563
0.598 Remote Similarity NPC477290
0.5977 Remote Similarity NPC82477
0.5977 Remote Similarity NPC142754
0.5977 Remote Similarity NPC296697
0.5977 Remote Similarity NPC39157
0.5974 Remote Similarity NPC64866
0.5962 Remote Similarity NPC184033
0.5955 Remote Similarity NPC304983
0.5955 Remote Similarity NPC223187
0.5946 Remote Similarity NPC328052
0.5941 Remote Similarity NPC314500
0.5934 Remote Similarity NPC65650
0.5921 Remote Similarity NPC145311
0.5918 Remote Similarity NPC168248
0.5914 Remote Similarity NPC228911
0.5914 Remote Similarity NPC469996
0.5914 Remote Similarity NPC169095
0.5914 Remote Similarity NPC74410
0.5914 Remote Similarity NPC115515
0.5909 Remote Similarity NPC286814
0.5909 Remote Similarity NPC61702
0.5909 Remote Similarity NPC162867
0.59 Remote Similarity NPC474844
0.5897 Remote Similarity NPC471751
0.5895 Remote Similarity NPC121984
0.5895 Remote Similarity NPC477372
0.5895 Remote Similarity NPC4166
0.5882 Remote Similarity NPC476753

  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 NPC477581 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.7 Intermediate Similarity NPD3527 Clinical (unspecified phase)
0.6941 Remote Similarity NPD4058 Approved
0.68 Remote Similarity NPD6404 Discontinued
0.6786 Remote Similarity NPD4691 Approved
0.6744 Remote Similarity NPD4687 Approved
0.6744 Remote Similarity NPD5733 Approved
0.6706 Remote Similarity NPD5276 Approved
0.6667 Remote Similarity NPD4137 Phase 3
0.6588 Remote Similarity NPD4747 Approved
0.6353 Remote Similarity NPD3621 Clinical (unspecified phase)
0.63 Remote Similarity NPD5769 Clinical (unspecified phase)
0.6064 Remote Similarity NPD8028 Phase 2
0.6049 Remote Similarity NPD287 Approved
0.6023 Remote Similarity NPD6939 Phase 2
0.6023 Remote Similarity NPD6938 Clinical (unspecified phase)
0.6 Remote Similarity NPD4096 Approved
0.5926 Remote Similarity NPD7812 Clinical (unspecified phase)
0.5918 Remote Similarity NPD5280 Approved
0.5918 Remote Similarity NPD4694 Approved
0.5833 Remote Similarity NPD4223 Phase 3
0.5833 Remote Similarity NPD4221 Approved
0.5758 Remote Similarity NPD5690 Phase 2
0.5758 Remote Similarity NPD5279 Phase 3
0.573 Remote Similarity NPD791 Approved
0.573 Remote Similarity NPD15 Approved
0.5714 Remote Similarity NPD3133 Approved
0.5714 Remote Similarity NPD3665 Phase 1
0.5714 Remote Similarity NPD3666 Approved
0.5714 Remote Similarity NPD4197 Approved
0.5699 Remote Similarity NPD1346 Approved
0.5691 Remote Similarity NPD6330 Clinical (unspecified phase)
0.5686 Remote Similarity NPD5692 Phase 3
0.5686 Remote Similarity NPD5207 Approved
0.5657 Remote Similarity NPD5329 Approved
0.5644 Remote Similarity NPD4518 Approved
0.5631 Remote Similarity NPD5694 Approved
0.5631 Remote Similarity NPD5281 Approved
0.5631 Remote Similarity NPD5284 Approved
0.5631 Remote Similarity NPD6050 Approved
0.5625 Remote Similarity NPD4695 Discontinued
0.56 Remote Similarity NPD7521 Approved
0.56 Remote Similarity NPD5205 Approved
0.56 Remote Similarity NPD7334 Approved
0.56 Remote Similarity NPD4689 Approved
0.56 Remote Similarity NPD4690 Approved
0.56 Remote Similarity NPD4623 Approved
0.56 Remote Similarity NPD3618 Phase 1
0.56 Remote Similarity NPD6684 Approved
0.56 Remote Similarity NPD4688 Approved
0.56 Remote Similarity NPD6409 Approved
0.56 Remote Similarity NPD4693 Phase 3
0.56 Remote Similarity NPD4138 Approved
0.56 Remote Similarity NPD3574 Clinical (unspecified phase)
0.56 Remote Similarity NPD7146 Approved
0.56 Remote Similarity NPD5330 Approved
0.56 Remote Similarity NPD4519 Discontinued

  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